ARID1A在肝癌侵袭转移中的作用及其机制研究
|
摘要
肝细胞癌（Hepatocellular carcinoma，HCC）（简称肝癌）是我国发病率最高的恶性肿瘤之一，虽然有关肝癌的研究已取得很大进展，但由于其极高的转移/复发率，肝癌病人总体5年生存率仅有5％左右。目前，肝肿瘤切除术和肝移植仍然是治疗肝细胞肝癌最有效的标准方案，因此，探索肝癌转移复发的机制，了解肿瘤的侵袭转移能力，预测患者预后，寻找有效的抑制途径，成为进一步提高肝癌患者生存率的关键。
肿瘤的发生发展、转移侵袭是一个复杂的、多因素作用的过程。从分子生物学的角度来看，肝癌是一种基因疾病。是某些染色体上的DNA损伤导致基因突变的结果，包括癌基因、抑癌基因、细胞凋亡基因、细胞周期调节基因、及维持细胞基因组稳定性的基因(如DNA修复、DNA复制及染色体分离基因)等，是一个多阶段逐步演化的过程。AT丰富结合域1A基因（theAT_rich interactivedomain1AARID1A）最早是作为染色质重塑复合物SWI／SNF (switch/sucrose non-fermenting)家族的一员被人们发现的。近年来的研究表明，它是一个重要的抑癌基因，与细胞增殖密切相关，在肿瘤的发生发展、转移复发过程中发挥重要作用。
至今，ARID1A对肝癌的影响尚未有明确报道。本实验主要研究ARID1A基因对肝癌生物学特性的影响。首先，检测ARID1A在40例肝癌及相应癌旁组织以及不同转移潜能肝癌细胞系中的表达差异;接着利用组织芯片技术对396例原发性肝癌手术切除的患者标本进行研究分析，研究ARID1A表达与肝癌发生、发展以及预后的相关性;通过转染与干扰调节ARID1A表达后,进行一系列体外和体内实验，研究ARID1A的表达对肝癌细胞生长增殖、侵袭转移方面的影响，最后探讨ARID1A抗肿瘤效应的可能机制，以期为防治肝癌提供新的靶点。
第一部分ARID1A在肝癌组织及肝癌细胞系中的表达研究
目的：研究ARID1A在肝癌细胞株，肝癌及相应癌旁组织中的表达差异，分析其与肝癌发生的关系。
方法：应用荧光定量PCR、Western Blot及免疫组织化学方法检测ARID1A在40例肝癌及相应的癌旁组织和正常肝组织中的表达。应用荧光定量PCR、免疫组织化学及Western Blot检测不同转移潜能肝癌细胞系中ARID1A的表达情况。
结果：Real-time RT-PCR检测结果分析显示：ARID1A基因在肝癌组织的相对表达量（0.005±0.0003）明显低于癌旁组织（0.0934±0.012），差异有统计学意义（P<0.05）。复发组肝癌组织（0.006±0.0001）ARID1A表达低于未复发组（0.023±0.005），差异有统计学意义（P<0.001）。复发组与未复发组的正常肝组织中ARID1A稳定表达，与预后无相关性。Western-Blot检测结果同样显示肝癌组织ARID1A基因表达低于癌旁组织，差异显著（P<0.05）。复发组与未复发组的正常肝组织中ARID1A稳定表达，与预后无相关性。在细胞研究中：免疫组化显示ARID1A表达情况与肝癌细胞系的转移潜能呈负相关（P<0.05）。Real-time PCR显示，ARID1A的表达，与肿瘤的恶性程度密切相关，ARID1A表达越高，肿瘤的恶性程度越低，ARID1A表达越低，肿瘤的恶性程度越高。
结论：ARID1A在肝癌发生、发展中可能有重要的作用
第二部分ARID1A表达与肝癌临床病例特征及相关性研究
目的：研究ARID1A基因在原发性肝癌中的表达情况，探讨ARID1A在肝癌及癌旁组织中的表达差异、相关性、与原发性肝癌的关系及临床意义。
方法：检测包含396例肝癌（癌旁）组织的组织芯片中ARID1A基因的表达情况，统计分析两者与肝癌临床病理特征及预后的关系。
结果：ARID1A蛋白的过表达与肝癌患者性别（P=0.036）、血管侵犯（P=0.193）、ALT（P=0.031）、Child-pugh分级（P=0.607)、BCLC stage（P=0.043）有关。ARID1A表达阳性组5年总体生存率及无病生存率明显高于ARID1A表达阴性组。分层Kaplan-Meier分析ARID1A表达显示：在高AFP组、肝硬化组、肿瘤大于5cm组中，肝癌组织中ARID1A过表达的患者OS和DFS高于低表达患者。多因素分析表明肿瘤大于5cm，有微血管侵犯，ARID1A表达阴性是影响OS的独立预后因素；肿瘤小于5cm，无微血管侵犯，ARID1A表达阳性是影响DFS的独立预后因素。
结论：肝癌组织中ARID1A的低表达与原发性肝癌的侵袭、转移及预后不良相关。
第三部分调节ARID1A基因表达对肝癌细胞侵袭与转移的影响及机制研究
目的：研究ARID1A与肝癌细胞侵袭、转移的关系及作用机制
方法：利用慢病毒质粒载体在M3和Hep-3B细胞株中分别转染促进ARID1A表达的TALE-VP64质粒和降低ARID1A表达的shARID1A干扰质粒，从而构建M3-ARID1A和Hep3B-shARID1A稳定细胞系。经Western-Blot，qRT-PCR验证ARID1A表达改变后，Transwell法研究细胞迁移、侵袭能力变化；MTT检测细胞增殖能力变化；流式细胞术检测细胞凋亡能力变化。同时研究ARID1A基因表达改变后，细胞中PTEN、PIK3CA、p53、MMP9、VEGF的表达变化；将细胞接种于裸鼠皮下建立成瘤模型，研究转染前后细胞成瘤能力变化，免疫组化检测裸鼠成瘤切片中PTEN，PIK3CA、p53、MMP9、VEGF的表达情况。
结果：慢病毒转染下调低转移能力的Hep3B细胞中ARID1A表达和上调高转移能力的HCCLM3细胞的ARID1A表达，建立稳定细胞株。ARID1A表达改变后，体外能明显改变肝癌细胞的迁移、侵袭、增殖和凋亡能力；体内能改变癌细胞成瘤能力。ARID1A上调后，PTEN、p53、PIK3CA基因表达均明显上调，而MMP9和VEGF基因表达均明显下调；ARID1A下调后，PTEN、p53、PIK3CA基因表达均明显下调，而MMP9和VEGF基因表达明显上调。证明ARID1A基因在肝癌中具有明显的抑癌作用。
结论：肝癌细胞ARID1A表达上调或下调能降低和促进肝癌的侵袭与转移的能力。
Hepatocellular carcinoma（HCC）is one of the highest incidence of malignant tumorsin China, Although much progress has been made in HCC research, but the invasion andmetastasis are the leading cause for the HCC death. Untill now, tumor resection and livertransplantation are the most effective and standard therapies for HCC, Therefore，it isessential to explore the underlying mechanisms of recurrence and metastasis of HCC tofind effective ways to improve the survival rate of HCC.
Tumor development, invasion and metastasis is a complex and dynamic processes.From the perspective of molecular biology, the HCC is a genetic disease. Because ofcertain chromosomes, DNA damage causes the mutation results in regulating genes,including oncogenes, tumor suppressor genes, apoptosis genes, cell cycle, and maintainthe stability of the cell genome gene is a multi-stage process of gradual evolution.Chromatin remodeling complexes SWI/SNF AT-rich interactive domain1A (ARID1A) isan important gene in cancer research in the past two years. It is an important tumorsuppressor gene and closely associated with cell proliferation.ARID1A play an importantrole in tumor development, metastasis and recurrence of the process.
There is no people had to reports of the impact in HCC. In the present study, wediscussed the impact of ARID1A on biological behaviors of HCC. We investigated theexpression of ARID1A in HCC Cell lines with different metastatic potential. Tissuemicroarray for240HCC patients showed decreased expression of ARID1A in tumor cellsand study with the development and prognosis in HCC. By in vivo and vitro experiment，we observed the impact of ARID1A expression on proliferation, invasion, tumor growthand metastasis. We hope to provide a new therapeutic target for the prevention andtreatment of HCC.
Part I The expression of CD88in hepatocellular carcinomaand HCC cell lines
Objective: We focused on the expression of CCRL1in cancer and peri-cancer tissuesand the relations between CCRL1expression and tumorigenesis.
Methods: We investigated the expression of ARID1A in HCC Cell lines withdifferent metastatic potential. Performed in cancer and peri-cancer tissue of40patientswho underwent HCC resection.
Result: We found that: ARID1A protein level detected by western blot wassignificantly lower in HCC than those in their adjacent nontumorous tissues（P<0.05）. theARID1A mRNA level Was significantly lower in HCC than those in their adjacentnontumorous tissues. The experiment in HCC cell lines, We found that: The level ofARID1A protein and mRNA in HCCLM3and MHCC-97H with high metastasis potentialwas lower than in Hep-G2and Hep-3B with low metastasis potential.
Conclusion: ARID1A play important role with the development in HCC
Part II Correlation and clinical significance of expressionof ARID1A in hepatocellular carcinoma
Objective: To investigate the correlation and clinical significance of ARID1A withHCC.
Methods: immunohistochemical staining was performed in tumor and peri-tumortissue of240patients who underwent HCC resection, then the clinical significance ofexpression of ARID1A was analyzed by SPSS16.0.
Result: Overexpression ARID1A was found to correlate significantly with high serumAFP level（P=0.031）, sex（P=0.036）, vascular invasion（P<0.0001）, Child-Pugh score（P=0.607). and BCLC stage（P=0.043）.5-year overall survival and disease-free survivalrate in the group of ARID1A-positive was significantly lowerthan that in the group ofARID1A-negative group(p<0.03). Multivariate analysis showed that serum AFP>20ng/ml, liver cirrhosis, Tumor size>5cm and ARID1A positive expression were independentprognostic factors for OS; serum AFP<20ng/ml, liver cirrhosis, Tumor size<5cm andpositive expression of ARID1A were independent prognostic factors for DFS.
Conclusion: The low expression of ARID1A can be a new marker in predicting theprognosis of HCC
Part III The impact on HCC biological characteristicsby regulation of ARID1A expression
Objective: Explore the impact of ARID1A on tumor growth, invasion, migration,apoptosisand metastasis in vivo and in vitro experiments.
Methods: Using lentivirus vector and TALE-VP64, we transfected shARID1Aknock-down and overexpression plasmids in Hep-3B and HCCLM3cell lines, toconstructed stable cell lines of Hep-3B-shARID1A and HCCLM3-ARID1A. theexpression of ARID1A was determined by qRT-PCR, western blot.The ability ofproliferation and invasion and migration was tested by MTT and transwell in the stabletransfection HCC cell and parental cell lines,The ability of apoptosis was tested by Flowcytometry. The human liver cancer mode was established with Hep-3B and HCCLM3cellsin athymic nude mouse. the gross tumor volumes were measured dynamically.Immunohistochemistry for the detection of tumer growth-related factor expression: PTEN，PIK3CA,p53，MMP9，VEGF.
Result: In vitro experiments, our results showed that: overexpression of ARID1Ainhibited the proliferation, migration and invasion of HCC cells. On the contrary,down-regulation of ARID1A caused the intensive proliferation, invasion, and migration ofHCC cells.HCC cell lines with high ARID1A expression increase the mRNA expression ofPTEN,p53,PIK3CA and decrease the mRNA expression of MMP9,VEGF.In vivo, thetumor mass in the low expression group higher than the high expression group.
Conclusion: ARID1A can inhibit the proliferation, migration and invasion of theHCC cell lins,overexpression ARID1A can increase the expression of PTEN,p53,PIK3CA and decrease the expression of MMP9,VEGF.
肿瘤的发生发展、转移侵袭是一个复杂的、多因素作用的过程。从分子生物学的角度来看，肝癌是一种基因疾病。是某些染色体上的DNA损伤导致基因突变的结果，包括癌基因、抑癌基因、细胞凋亡基因、细胞周期调节基因、及维持细胞基因组稳定性的基因(如DNA修复、DNA复制及染色体分离基因)等，是一个多阶段逐步演化的过程。AT丰富结合域1A基因（theAT_rich interactivedomain1AARID1A）最早是作为染色质重塑复合物SWI／SNF (switch/sucrose non-fermenting)家族的一员被人们发现的。近年来的研究表明，它是一个重要的抑癌基因，与细胞增殖密切相关，在肿瘤的发生发展、转移复发过程中发挥重要作用。
至今，ARID1A对肝癌的影响尚未有明确报道。本实验主要研究ARID1A基因对肝癌生物学特性的影响。首先，检测ARID1A在40例肝癌及相应癌旁组织以及不同转移潜能肝癌细胞系中的表达差异;接着利用组织芯片技术对396例原发性肝癌手术切除的患者标本进行研究分析，研究ARID1A表达与肝癌发生、发展以及预后的相关性;通过转染与干扰调节ARID1A表达后,进行一系列体外和体内实验，研究ARID1A的表达对肝癌细胞生长增殖、侵袭转移方面的影响，最后探讨ARID1A抗肿瘤效应的可能机制，以期为防治肝癌提供新的靶点。
第一部分ARID1A在肝癌组织及肝癌细胞系中的表达研究
目的：研究ARID1A在肝癌细胞株，肝癌及相应癌旁组织中的表达差异，分析其与肝癌发生的关系。
方法：应用荧光定量PCR、Western Blot及免疫组织化学方法检测ARID1A在40例肝癌及相应的癌旁组织和正常肝组织中的表达。应用荧光定量PCR、免疫组织化学及Western Blot检测不同转移潜能肝癌细胞系中ARID1A的表达情况。
结果：Real-time RT-PCR检测结果分析显示：ARID1A基因在肝癌组织的相对表达量（0.005±0.0003）明显低于癌旁组织（0.0934±0.012），差异有统计学意义（P<0.05）。复发组肝癌组织（0.006±0.0001）ARID1A表达低于未复发组（0.023±0.005），差异有统计学意义（P<0.001）。复发组与未复发组的正常肝组织中ARID1A稳定表达，与预后无相关性。Western-Blot检测结果同样显示肝癌组织ARID1A基因表达低于癌旁组织，差异显著（P<0.05）。复发组与未复发组的正常肝组织中ARID1A稳定表达，与预后无相关性。在细胞研究中：免疫组化显示ARID1A表达情况与肝癌细胞系的转移潜能呈负相关（P<0.05）。Real-time PCR显示，ARID1A的表达，与肿瘤的恶性程度密切相关，ARID1A表达越高，肿瘤的恶性程度越低，ARID1A表达越低，肿瘤的恶性程度越高。
结论：ARID1A在肝癌发生、发展中可能有重要的作用
第二部分ARID1A表达与肝癌临床病例特征及相关性研究
目的：研究ARID1A基因在原发性肝癌中的表达情况，探讨ARID1A在肝癌及癌旁组织中的表达差异、相关性、与原发性肝癌的关系及临床意义。
方法：检测包含396例肝癌（癌旁）组织的组织芯片中ARID1A基因的表达情况，统计分析两者与肝癌临床病理特征及预后的关系。
结果：ARID1A蛋白的过表达与肝癌患者性别（P=0.036）、血管侵犯（P=0.193）、ALT（P=0.031）、Child-pugh分级（P=0.607)、BCLC stage（P=0.043）有关。ARID1A表达阳性组5年总体生存率及无病生存率明显高于ARID1A表达阴性组。分层Kaplan-Meier分析ARID1A表达显示：在高AFP组、肝硬化组、肿瘤大于5cm组中，肝癌组织中ARID1A过表达的患者OS和DFS高于低表达患者。多因素分析表明肿瘤大于5cm，有微血管侵犯，ARID1A表达阴性是影响OS的独立预后因素；肿瘤小于5cm，无微血管侵犯，ARID1A表达阳性是影响DFS的独立预后因素。
结论：肝癌组织中ARID1A的低表达与原发性肝癌的侵袭、转移及预后不良相关。
第三部分调节ARID1A基因表达对肝癌细胞侵袭与转移的影响及机制研究
目的：研究ARID1A与肝癌细胞侵袭、转移的关系及作用机制
方法：利用慢病毒质粒载体在M3和Hep-3B细胞株中分别转染促进ARID1A表达的TALE-VP64质粒和降低ARID1A表达的shARID1A干扰质粒，从而构建M3-ARID1A和Hep3B-shARID1A稳定细胞系。经Western-Blot，qRT-PCR验证ARID1A表达改变后，Transwell法研究细胞迁移、侵袭能力变化；MTT检测细胞增殖能力变化；流式细胞术检测细胞凋亡能力变化。同时研究ARID1A基因表达改变后，细胞中PTEN、PIK3CA、p53、MMP9、VEGF的表达变化；将细胞接种于裸鼠皮下建立成瘤模型，研究转染前后细胞成瘤能力变化，免疫组化检测裸鼠成瘤切片中PTEN，PIK3CA、p53、MMP9、VEGF的表达情况。
结果：慢病毒转染下调低转移能力的Hep3B细胞中ARID1A表达和上调高转移能力的HCCLM3细胞的ARID1A表达，建立稳定细胞株。ARID1A表达改变后，体外能明显改变肝癌细胞的迁移、侵袭、增殖和凋亡能力；体内能改变癌细胞成瘤能力。ARID1A上调后，PTEN、p53、PIK3CA基因表达均明显上调，而MMP9和VEGF基因表达均明显下调；ARID1A下调后，PTEN、p53、PIK3CA基因表达均明显下调，而MMP9和VEGF基因表达明显上调。证明ARID1A基因在肝癌中具有明显的抑癌作用。
结论：肝癌细胞ARID1A表达上调或下调能降低和促进肝癌的侵袭与转移的能力。
Hepatocellular carcinoma（HCC）is one of the highest incidence of malignant tumorsin China, Although much progress has been made in HCC research, but the invasion andmetastasis are the leading cause for the HCC death. Untill now, tumor resection and livertransplantation are the most effective and standard therapies for HCC, Therefore，it isessential to explore the underlying mechanisms of recurrence and metastasis of HCC tofind effective ways to improve the survival rate of HCC.
Tumor development, invasion and metastasis is a complex and dynamic processes.From the perspective of molecular biology, the HCC is a genetic disease. Because ofcertain chromosomes, DNA damage causes the mutation results in regulating genes,including oncogenes, tumor suppressor genes, apoptosis genes, cell cycle, and maintainthe stability of the cell genome gene is a multi-stage process of gradual evolution.Chromatin remodeling complexes SWI/SNF AT-rich interactive domain1A (ARID1A) isan important gene in cancer research in the past two years. It is an important tumorsuppressor gene and closely associated with cell proliferation.ARID1A play an importantrole in tumor development, metastasis and recurrence of the process.
There is no people had to reports of the impact in HCC. In the present study, wediscussed the impact of ARID1A on biological behaviors of HCC. We investigated theexpression of ARID1A in HCC Cell lines with different metastatic potential. Tissuemicroarray for240HCC patients showed decreased expression of ARID1A in tumor cellsand study with the development and prognosis in HCC. By in vivo and vitro experiment，we observed the impact of ARID1A expression on proliferation, invasion, tumor growthand metastasis. We hope to provide a new therapeutic target for the prevention andtreatment of HCC.
Part I The expression of CD88in hepatocellular carcinomaand HCC cell lines
Objective: We focused on the expression of CCRL1in cancer and peri-cancer tissuesand the relations between CCRL1expression and tumorigenesis.
Methods: We investigated the expression of ARID1A in HCC Cell lines withdifferent metastatic potential. Performed in cancer and peri-cancer tissue of40patientswho underwent HCC resection.
Result: We found that: ARID1A protein level detected by western blot wassignificantly lower in HCC than those in their adjacent nontumorous tissues（P<0.05）. theARID1A mRNA level Was significantly lower in HCC than those in their adjacentnontumorous tissues. The experiment in HCC cell lines, We found that: The level ofARID1A protein and mRNA in HCCLM3and MHCC-97H with high metastasis potentialwas lower than in Hep-G2and Hep-3B with low metastasis potential.
Conclusion: ARID1A play important role with the development in HCC
Part II Correlation and clinical significance of expressionof ARID1A in hepatocellular carcinoma
Objective: To investigate the correlation and clinical significance of ARID1A withHCC.
Methods: immunohistochemical staining was performed in tumor and peri-tumortissue of240patients who underwent HCC resection, then the clinical significance ofexpression of ARID1A was analyzed by SPSS16.0.
Result: Overexpression ARID1A was found to correlate significantly with high serumAFP level（P=0.031）, sex（P=0.036）, vascular invasion（P<0.0001）, Child-Pugh score（P=0.607). and BCLC stage（P=0.043）.5-year overall survival and disease-free survivalrate in the group of ARID1A-positive was significantly lowerthan that in the group ofARID1A-negative group(p<0.03). Multivariate analysis showed that serum AFP>20ng/ml, liver cirrhosis, Tumor size>5cm and ARID1A positive expression were independentprognostic factors for OS; serum AFP<20ng/ml, liver cirrhosis, Tumor size<5cm andpositive expression of ARID1A were independent prognostic factors for DFS.
Conclusion: The low expression of ARID1A can be a new marker in predicting theprognosis of HCC
Part III The impact on HCC biological characteristicsby regulation of ARID1A expression
Objective: Explore the impact of ARID1A on tumor growth, invasion, migration,apoptosisand metastasis in vivo and in vitro experiments.
Methods: Using lentivirus vector and TALE-VP64, we transfected shARID1Aknock-down and overexpression plasmids in Hep-3B and HCCLM3cell lines, toconstructed stable cell lines of Hep-3B-shARID1A and HCCLM3-ARID1A. theexpression of ARID1A was determined by qRT-PCR, western blot.The ability ofproliferation and invasion and migration was tested by MTT and transwell in the stabletransfection HCC cell and parental cell lines,The ability of apoptosis was tested by Flowcytometry. The human liver cancer mode was established with Hep-3B and HCCLM3cellsin athymic nude mouse. the gross tumor volumes were measured dynamically.Immunohistochemistry for the detection of tumer growth-related factor expression: PTEN，PIK3CA,p53，MMP9，VEGF.
Result: In vitro experiments, our results showed that: overexpression of ARID1Ainhibited the proliferation, migration and invasion of HCC cells. On the contrary,down-regulation of ARID1A caused the intensive proliferation, invasion, and migration ofHCC cells.HCC cell lines with high ARID1A expression increase the mRNA expression ofPTEN,p53,PIK3CA and decrease the mRNA expression of MMP9,VEGF.In vivo, thetumor mass in the low expression group higher than the high expression group.
Conclusion: ARID1A can inhibit the proliferation, migration and invasion of theHCC cell lins,overexpression ARID1A can increase the expression of PTEN,p53,PIK3CA and decrease the expression of MMP9,VEGF.
引文
1. Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treatinghepatocellular carcinoma. CA Cancer J Clin.2012.62(6):394-9.
2. Jemal A,Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CACancer J Clin.2011.61(2):69-90.
3. Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, et al. A decade's studies onmetastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol2004;130:187-196.
4. El-SeragHB,Rudolph KL. Hepatocellular carcinoma: epidemiology and molecularcarcinogenesis. Gastroenterology.2007.132(7):2557-76.
5. Lope CR,Tremosini S,Forner A, Reig M, Bruix J. Management of HCC. J Hepatol.2012.56Suppl1: S75-87.
6. Llovet JM,Bruix J. Molecular targeted therapies in hepatocellular carcinoma.Hepatology.2008,48:1312-27.
7. Mandel, S. Gozes, I. et al. Activity-dependent neuroprotective protein constitutes anovel element in the SWI/SNF chromatin remodeling complex.J Biol Chem.2007282(47):34448-56.
8. D. Reisman, S. Glaros and E.A.Thompson.The SWI/SNF complex andcancer.Oncogene,2009,28(14):1653-1668
9. B. G. Wilson and C. W. Roberts.SWI/SNF nucleosome remodellers and cancer.NatRev Cancer,2011,11(7):481-492
10. O.I.Kulaeva,D.A.Gaykalova and V. M. Studitsky.Transcription through chromatin byRNA polymerase II: histone displacement and exchange [J].MutatRes,2007,618(1-2):116-129
11. D. J. Tremethick.Higher-order structures of chromatin: the elusive30nm fiber[J].Cell,2007,128(4):651-654
12. A. S. Yoo and G. R. Crabtree.ATP-dependent chromatin remodeling in neuraldevelopment [J].Curr Opin Neurobiol,2009,19(2):120-126
13. B. Weissman and K. E. Knudsen.Hijacking the chromatin remodeling machinery:impact of SWI/SNF perturbations in cancer [J].Cancer Res,2009,69(21):8223-8230
14. P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
15. F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
16. P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
17. D. J. Birnbaum, R. Sabatier, E. Mamessier, et al.[An "ariditary" form of ovariancancer][J].Med Sci (Paris),2010,26(12):1040-1042
18. K. Wang, J. Kan, S. T. Yuen, et al.Exome sequencing identifies frequent mutation ofARID1A in molecular subtypes of gastric cancer [J].Nat Genet,2011,43(12):1219-1223
19. S. Jones, T. L. Wang, M. Shih Ie, et al.Frequent mutations of chromatin remodelinggene ARID1A in ovarian clear cell carcinoma [J].Science,2010,330(6001):228-231
20. J. S. Seo, Y. S. Ju, W. C. Lee, et al.The transcriptional landscape and mutationalprofile of lung adenocarcinoma [J].Genome Res,2012,22(11):2109-2119
21. X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].Cancer Epidemiol,2012,36(3):288-293
22. Y. Gui, G. Guo, Y. Huang, et al.Frequent mutations of chromatin remodeling genes intransitional cell carcinoma of the bladder [J].Nat Genet,2011,43(9):875-878
23. A. V. Biankin, N. Waddell, K. S. Kassahn, et al.Pancreatic cancer genomes revealaberrations in axon guidance pathway genes [J].Nature,2012,491(7424):399-405
24. F. Mitelman, F. Mertens and B. Johansson.A breakpoint map of recurrentchromosomal rearrangements in human neoplasia [J].Nat Genet,1997,15SpecNo:417-474
25. B. Weissman and K. E. Knudsen.Hijacking the chromatin remodeling machinery:impact of SWI/SNF perturbations in cancer [J]. Cancer Res,2009,69(21):8223-8230
26. C. Guichard, G. Amaddeo, S. Imbeaud, et al.Integrated analysis of somatic mutationsand focal copy-number changes identifies key genes and pathways in hepatocellularcarcinoma [J].Nat Genet,2012,44(6):694-698
27. A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
1. D. Reisman, S. Glaros and E. A. Thompson.The SWI/SNF complex and cancer[J].Oncogene,2009,28(14):1653-1668
2. B. G. Wilson and C. W. Roberts.SWI/SNF nucleosome remodellers and cancer [J].NatRev Cancer,2011,11(7):481-492
3. F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
4. N. G. Nagl, Jr., A. Patsialou, D. S. Haines, et al.The p270(ARID1A/SMARCF1)subunit of mammalian SWI/SNF-related complexes is essential for normal cell cyclearrest [J].Cancer Res,2005,65(20):9236-9244
5. Bruix J,Sherman M.Management of hepatocellular carcinoma: an update. Hepatology.2011.53(3):1020-2.
6. C. L. Peterson and I. Herskowitz.Characterization of the yeast SWI1, SWI2, and SWI3genes, which encode a global activator of transcription [J].Cell,1992,68(3):573-583
7. O. I. Kulaeva, D. A. Gaykalova and V. M. Studitsky.Transcription through chromatinby RNA polymerase II: histone displacement and exchange [J].MutatRes,2007,618(1-2):116-129
8. D. J. Tremethick.Higher-order structures of chromatin: the elusive30nm fiber[J].Cell,2007,128(4):651-654
9. N. G. Nagl, Jr., A. Patsialou, D. S. Haines, et al.The p270(ARID1A/SMARCF1)subunit of mammalian SWI/SNF-related complexes is essential for normal cell cyclearrest [J].Cancer Res,2005,65(20):9236-9244
10. X.Wang, N.G.Nagl, Jr., S. Flowers, et al.Expression of p270(ARID1A), a componentof human SWI/SNF complexes, in human tumors [J].Int J Cancer,2004,112(4):636
11. W.Wang,T.Chi,Y.Xue,etal. Architectural DNA binding by ahigh-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes[J].Proc Natl Acad Sci U S A,1998,95(2):492-498
12. J. I. Wu, J. Lessard and G. R. Crabtree.Understanding the words of chromatinregulation [J].Cell,2009,136(2):200-206
13. X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].CancerEpidemiol,2012,36(3):288-293
14. D. D. Wang, Y. B. Chen, K. Pan, et al.Decreased expression of the ARID1A gene isassociated with poor prognosis in primary gastric cancer [J].PLoSOne,2012,7(7):e40364
15. C. Guichard, G. Amaddeo, S. Imbeaud, et al.Integrated analysis of somatic mutationsand focal copy-number changes identifies key genes and pathways in hepatocellularcarcinoma [J].Nat Genet,2012,44(6):694-698
16. A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
1F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
2P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
3A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
4Kononen,J.,et al.,Tissue microarrays for high-throughput molecular Profiling of tumorspecimens.Nat Med,1998.4(7):p.844-7.
5Gao, Q., et al.,Intraturnoral balance of regulatory and cytotoxic T cells is Associatedwith Prognosis of hepatocellular carcinoma after resection. J Clin Oncol,2007.25(18):P.2586-93
6S. Jones, T. L. Wang, M. Shih Ie, et al.Frequent mutations of chromatin remodelinggene ARID1A in ovarian clear cell carcinoma [J].Science,2010,330(6001):228-231
7Z. J. Zang, I. Cutcutache, S. L. Poon, et al.Exome sequencing of gastricadenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatinremodeling genes [J].Nat Genet,2012,44(5):570-574
8D. J. Birnbaum, J. Adelaide, E. Mamessier, et al.Genome profiling of pancreaticadenocarcinoma [J].Genes Chromosomes Cancer,2011,50(6):456-465
9X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].CancerEpidemiol,2012,36(3):288-293
10J.S. Seo, Y. S. Ju, W. C. Lee, et al.The transcriptional landscape and mutational profileof lung adenocarcinoma [J].Genome Res,2012,22(11):2109-2119
11X. Wang, N. G. Nagl, Jr., S. Flowers, et al.Expression of p270(ARID1A), acomponent of human SWI/SNF complexes, in human tumors [J].Int JCancer,2004,112(4):636
12T. Takeuchi, S. Nicole, A. Misaki, et al.Expression of SMARCF1, a truncated form ofSWI1, in neuroblastoma [J].Am J Pathol,2001,158(2):663-672
13N. Cancer Genome Atlas.Comprehensive molecular characterization of human colonand rectal cancer [J].Nature,2012,487(7407):330-337
1. Ghassan Allo, Marcus Q Bernardini ARID1Aloss correlates with mismatch repairdeficiency and intact p53expression in high-grade endometrial carcinomas [J] ModernPathology(2013),1–7
2. Tsui-Lien Mao, Ie-Ming Shih. The roles of ARID1A in gynecologic cancer.[J] JGynecol Oncol.2013.24（4）：376
3. S. Yamamoto, H. Tsuda, M. Takano, et al.Loss of ARID1A protein expression occursas an early event in ovarian clear-cell carcinoma development and frequently coexistswith PIK3CA mutations [J].Mod Pathol,2012,25(4):615-624
4. K. Wang, J. Kan, S. T. Yuen, et al.Exome sequencing identifies frequent mutation ofARID1A in molecular subtypes of gastric cancer [J].Nat Genet,2011,43(12):1219-1223
5. Hollander MC, Blumenthal GM, Dennis PA.2011. PTEN loss in the continuum ofcommon cancers, rare syndromes and mouse models.[J] Nat Rev Cancer11:289–301
6. Han Liang,1,9,11Lydia W.T. Cheung, Whole-exome sequencing combined withfunctional genomics reveals novel candidate driver cancer genes in endometrial cancer,[J].Genome Res.201222:2120-2129
7. Bin Guan, Tian-Li Wang, Ie-Ming Shih.ARID1A, a Factor That Promotes Formationof SWI/SNFMediated Chromatin Remodeling, Is a Tumor Suppressor in GynecologicCancers.[J].American Association for Cancer Research.2011;DOI:10.1158/0008-5472
8. Devita VT, Hellman S, Rosenberg SA. Cancer: Principies and practice of oncology.5th eds. Philadelphia:[J] Lippincott-Raven Publishers.1997,79-102.
9. Wong CW, Lee A, Shientag L. Apoptosis: an early event in metastatic inefficiency.[J].Cancer Research.2001,61(1):333-338.
10. Li SY, Yu B, An P, et al. Influence of FasL gene expression on hepatic metastasis ofcolorectal carcinoma.[J]. Hepa Panc D Int.2004,3(2):226-229.
11. Bernstorff WV, Glick MJ, Odze RD, et al. Fas(CD95/APO-1) and Fas ligandexpression in normal pancreas and pancreatic tumors. Implications for immuneprivilege and immune escape.[J].Cancer.2002,94(10):2552-2560.
12. Shen WH, Balajee AS, Wang J. Essential role for nuclear PTEN in maintainingchromosomal integrity.[J].Mol Cell,2007,128(1):157-170．
13. Baker SJ. PTEN enters the nuclear age.[J].Mol Cell,2007,128(1)：25-28．
14. Tamguney T, Stokoe D. New insight into PTEN．[J].Cell Science,2007,120(23)：4071-4079.
15. Planchon SM, Waite KA, Eng C. The nuclear affairs of PTEN.[J].Cell Science.2008,121:249-253．
16. Liu JL, Sheng X, Hortobaryi ZK, et a1. Nuclear PTEN-Mediated growth suppressionis independent of Akt down-regulation.[J]. MolCell Biol.2005,25(7):6211-6224.
17. Zhong H, Chiles K, Feldser D, et a1. Modulation of hypoxia-inducible factor1alphaexpression by the epidermal growth factor/phosphatidylinositol3-kinase/PTEN/AKT/FRAP path-way in human prostate cancer cells:implications for tumorangiogenesis and therapeutics.[J].Cancer Res.2000,60(6):1541-1545.
18. Hara S, Oya M, Mizuno R, et a1. Akt activation in renal cell carcinoma: Contributionof a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor.[J].Ann Oncol.2005,16(6):928-933.
19. Hamada K, Sasaki T, Koni P A, et a1. The PTEN/PI3K pathway governs normalvascular development and tumor angiogenesis.[J].Genes Dev.2005,19(17):2054-2065
20.21Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway intumor growth and angiogenesis.[J].J Clin Oncol.2005,23(5):1011-1027.
21. Marrogi AJ, Travis WD, Welsh JA, et al. Nitric oxide synthase, cyclooxygenase2, andvascular endothelial growth factor in the angiogenesis of non-small cell lungcarcinoma.[J]. Clin Can Res.2000,6(12):4739-4744.
1. P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
2. B. Guan, M. Gao, C. H. Wu, et al.Functional Analysis of In-frame Indel ARID1AMutations Reveals New Regulatory Mechanisms of Its Tumor Suppressor Functions[J].Neoplasia,2012,14(10):986-993
3. D. J. Birnbaum, R. Sabatier, E. Mamessier, et al.[An "ariditary" form of ovariancancer][J].Med Sci (Paris),2010,26(12):1040-1042
4. S. Jones, T. L. Wang, M. Shih Ie, et al.Frequent mutations of chromatin remodelinggene ARID1A in ovarian clear cell carcinoma [J].Science,2010,330(6001):228-231
5. K. Wang, J. Kan, S. T. Yuen, et al.Exome sequencing identifies frequent mutation ofARID1A in molecular subtypes of gastric cancer [J].Nat Genet,2011,43(12):1219-1223
6. J. S. Seo, Y. S. Ju, W. C. Lee, et al.The transcriptional landscape and mutationalprofile of lung adenocarcinoma [J].Genome Res,2012,22(11):2109-2119
7. X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].CancerEpidemiol,2012,36(3):288-293
8. A. V. Biankin, N. Waddell, K. S. Kassahn, et al.Pancreatic cancer genomes revealaberrations in axon guidance pathway genes [J].Nature,2012,491(7424):399-405
9. Y. Gui, G. Guo, Y. Huang, et al.Frequent mutations of chromatin remodeling genesin transitional cell carcinoma of the bladder [J].Nat Genet,2011,43(9):875-878
10. F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
11. F. Mitelman, F. Mertens and B. Johansson.A breakpoint map of recurrentchromosomal rearrangements in human neoplasia [J].Nat Genet,1997,15SpecNo:417-474
12. B. Weissman and K. E. Knudsen.Hijacking the chromatin remodeling machinery:impact of SWI/SNF perturbations in cancer [J].Cancer Res,2009,69(21):8223-8230
13. C. L. Peterson and I. Herskowitz.Characterization of the yeast SWI1, SWI2, and SWI3genes, which encode a global activator of transcription [J].Cell,1992,68(3):573-583
14. Z. Kozmik, O. Machon, J. Kralova, et al.Characterization of mammalian orthologuesof the Drosophila osa gene: cDNA cloning, expression, chromosomal localization, anddirect physical interaction with Brahma chromatin-remodeling complex[J].Genomics,2001,73(2):140-148
15. C. Muchardt and M. Yaniv.ATP-dependent chromatin remodelling: SWI/SNF and Co.are on the job [J].J Mol Biol,1999,293(2):187-198
16. O. I. Kulaeva, D. A. Gaykalova and V. M. Studitsky.Transcription through chromatinby RNA polymerase II: histone displacement and exchange [J].MutatRes,2007,618(1-2):116-129
17. D. J. Tremethick.Higher-order structures of chromatin: the elusive30nm fiber[J].Cell,2007,128(4):651-654
18. A. S. Yoo and G. R. Crabtree.ATP-dependent chromatin remodeling in neuraldevelopment [J].Curr Opin Neurobiol,2009,19(2):120-126
19. N. G. Nagl, Jr., A. Patsialou, D. S. Haines, et al.The p270(ARID1A/SMARCF1)subunit of mammalian SWI/SNF-related complexes is essential for normal cell cyclearrest [J].Cancer Res,2005,65(20):9236-9244
20. Z. Nie, Y. Xue, D. Yang, et al.A specificity and targeting subunit of a humanSWI/SNF family-related chromatin-remodeling complex [J].Mol CellBiol,2000,20(23):8879-8888
21. W. Wang, T. Chi, Y. Xue, et al.Architectural DNA binding by ahigh-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes[J].Proc Natl Acad Sci U S A,1998,95(2):492-498
22. J. I. Wu, J. Lessard and G. R. Crabtree.Understanding the words of chromatinregulation [J].Cell,2009,136(2):200-206
23. D. Reisman, S. Glaros and E. A. Thompson.The SWI/SNF complex and cancer[J].Oncogene,2009,28(14):1653-1668
24. B. G. Wilson and C. W. Roberts.SWI/SNF nucleosome remodellers and cancer [J].NatRev Cancer,2011,11(7):481-492
25. X. Wang, N. G. Nagl, Jr., S. Flowers, et al.Expression of p270(ARID1A), acomponent of human SWI/SNF complexes, in human tumors [J].Int JCancer,2004,112(4):636
26. E. Crow, Z. Du and L. Li.New insights into prion biology from the novel [SWI+]system [J].Prion,2008,2(4):141-144
27.[27] X. S. Li, P. Trojer, T. Matsumura, et al.Mammalian SWI/SNF--a subunitBAF250/ARID1is an E3ubiquitin ligase that targets histone H2B [J].Mol CellBiol,2010,30(7):1673-1688
28. B. Vogelstein and K. W. Kinzler.Cancer genes and the pathways they control [J].NatMed,2004,10(8):789-799
29. S. Rodriguez-Nieto and M. Sanchez-Cespedes.BRG1and LKB1: tales of two tumorsuppressor genes on chromosome19p and lung cancer [J].Carcinogenesis,2009,30(4):547-554
30. W. J. Lowery, J. M. Schildkraut, L. Akushevich, et al.Loss of ARID1A-associatedprotein expression is a frequent event in clear cell and endometrioid ovarian cancers[J].Int J Gynecol Cancer,2012,22(1):9-14
31. E. P. Samartzis, N. Samartzis, A. Noske, et al.Loss of ARID1A/BAF250a-expressionin endometriosis: a biomarker for risk of carcinogenic transformation?[J].ModPathol,2012,25(6):885-892
32. W. Xiao, A. Awadallah and W. Xin.Loss of ARID1A/BAF250a expression in ovarianendometriosis and clear cell carcinoma [J].Int J Clin Exp Pathol,2012,5(7):642-650
33. K. C. Wiegand, S. P. Shah, O. M. Al-Agha, et al.ARID1A mutations inendometriosis-associated ovarian carcinomas [J]. N Engl J Med,2010,363(16):1532-1543
34. A. Ayhan, T. L. Mao, T. Seckin, et al.Loss of ARID1A Expression Is an EarlyMolecular Event in Tumor Progression From Ovarian Endometriotic Cyst to ClearCell and Endometrioid Carcinoma [J].Int J Gynecol Cancer,2012,22(8):1310-1315
35. H. M. Werner, A. Berg, E. Wik, et al.ARID1A loss is prevalent in endometrialhyperplasia with atypia and low-grade endometrioid carcinomas [J].Mod Pathol,2012
36. D. J. Birnbaum, D. Birnbaum and F. Bertucci.Endometriosis-associated ovariancarcinomas [J].N Engl J Med,2011,364(5):483-4; author reply484-485
37. A. Katagiri, K. Nakayama, M. T. Rahman, et al.Frequent loss of tumor suppressorARID1A protein expression in adenocarcinomas/adenosquamous carcinomas of theuterine cervix [J].Int J Gynecol Cancer,2012,22(2):208-212
38. S. Yamamoto, H. Tsuda, M. Takano, et al.Loss of ARID1A protein expression occursas an early event in ovarian clear-cell carcinoma development and frequently coexistswith PIK3CA mutations [J].Mod Pathol,2012,25(4):615-624
39. A. Katagiri, K. Nakayama, M. T. Rahman, et al.Loss of ARID1A expression is relatedto shorter progression-free survival and chemoresistance in ovarian clear cellcarcinoma [J].Mod Pathol,2012,25(2):282-288
40. Z. J. Zang, I. Cutcutache, S. L. Poon, et al.Exome sequencing of gastricadenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatinremodeling genes [J].Nat Genet,2012,44(5):570-574
41. S. Jones, M. Li, D. W. Parsons, et al.Somatic mutations in the chromatin remodelinggene ARID1A occur in several tumor types [J].Hum Mutat,2012,33(1):100-103
42. D. D. Wang, Y. B. Chen, K. Pan, et al.Decreased expression of the ARID1A gene isassociated with poor prognosis in primary gastric cancer [J].PLoS One,2012,7(7):e40364
43. D. J. Birnbaum, J. Adelaide, E. Mamessier, et al.Genome profiling of pancreaticadenocarcinoma [J].Genes Chromosomes Cancer,2011,50(6):456-465
44. A. H. Shain, C. P. Giacomini, K. Matsukuma, et al.Convergent structural alterationsdefine SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a centraltumor suppressive complex in pancreatic cancer [J].Proc Natl Acad Sci U SA,2012,109(5):E252-259
45. C. Guichard, G. Amaddeo, S. Imbeaud, et al.Integrated analysis of somatic mutationsand focal copy-number changes identifies key genes and pathways in hepatocellularcarcinoma [J].Nat Genet,2012,44(6):694-698
46. A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
47. J. Huang, Y. L. Zhao, Y. Li, et al.Genomic and functional evidence for an ARID1Atumor suppressor role [J].Genes Chromosomes Cancer,2007,46(8):745-750
48. T. Takeuchi, S. Nicole, A. Misaki, et al.Expression of SMARCF1, a truncated form ofSWI1, in neuroblastoma [J].Am J Pathol,2001,158(2):663-672
49. D. W. Serber, A. Rogala, M. Makarem, et al.The BRG1chromatin remodeler protectsagainst ovarian cysts, uterine tumors, and mammary tumors in a lineage-specificmanner [J].PLoS One,2012,7(2):e31346
50. Z. Nie, Z. Yan, E. H. Chen, et al.Novel SWI/SNF chromatin-remodeling complexescontain a mixed-lineage leukemia chromosomal translocation partner [J].Mol CellBiol,2003,23(8):2942-2952
51. L. Giulino-Roth, K. Wang, T. Y. Macdonald, et al.Targeted genomic sequencing ofpediatric Burkitt lymphoma identifies recurrent alterations in anti-apoptotic andchromatin-remodeling genes [J].Blood,2012
52. N. Cancer Genome Atlas.Comprehensive molecular characterization of human colonand rectal cancer [J].Nature,2012,487(7407):330-337
53. S. Yamamoto, H. Tsuda, M. Takano, et al.PIK3CA mutations and loss of ARID1Aprotein expression are early events in the development of cystic ovarian clear celladenocarcinoma [J].Virchows Arch,2012,460(1):77-87
54. Eleftherios P. Samartzis, Aurelia Noske, Konstantin J. Dedes.ARID1AMutations andPI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-AssociatedOvarian Carcinomas Int. J. Mol. Sci.2013,14,18824-18849
2. Jemal A,Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CACancer J Clin.2011.61(2):69-90.
3. Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, et al. A decade's studies onmetastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol2004;130:187-196.
4. El-SeragHB,Rudolph KL. Hepatocellular carcinoma: epidemiology and molecularcarcinogenesis. Gastroenterology.2007.132(7):2557-76.
5. Lope CR,Tremosini S,Forner A, Reig M, Bruix J. Management of HCC. J Hepatol.2012.56Suppl1: S75-87.
6. Llovet JM,Bruix J. Molecular targeted therapies in hepatocellular carcinoma.Hepatology.2008,48:1312-27.
7. Mandel, S. Gozes, I. et al. Activity-dependent neuroprotective protein constitutes anovel element in the SWI/SNF chromatin remodeling complex.J Biol Chem.2007282(47):34448-56.
8. D. Reisman, S. Glaros and E.A.Thompson.The SWI/SNF complex andcancer.Oncogene,2009,28(14):1653-1668
9. B. G. Wilson and C. W. Roberts.SWI/SNF nucleosome remodellers and cancer.NatRev Cancer,2011,11(7):481-492
10. O.I.Kulaeva,D.A.Gaykalova and V. M. Studitsky.Transcription through chromatin byRNA polymerase II: histone displacement and exchange [J].MutatRes,2007,618(1-2):116-129
11. D. J. Tremethick.Higher-order structures of chromatin: the elusive30nm fiber[J].Cell,2007,128(4):651-654
12. A. S. Yoo and G. R. Crabtree.ATP-dependent chromatin remodeling in neuraldevelopment [J].Curr Opin Neurobiol,2009,19(2):120-126
13. B. Weissman and K. E. Knudsen.Hijacking the chromatin remodeling machinery:impact of SWI/SNF perturbations in cancer [J].Cancer Res,2009,69(21):8223-8230
14. P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
15. F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
16. P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
17. D. J. Birnbaum, R. Sabatier, E. Mamessier, et al.[An "ariditary" form of ovariancancer][J].Med Sci (Paris),2010,26(12):1040-1042
18. K. Wang, J. Kan, S. T. Yuen, et al.Exome sequencing identifies frequent mutation ofARID1A in molecular subtypes of gastric cancer [J].Nat Genet,2011,43(12):1219-1223
19. S. Jones, T. L. Wang, M. Shih Ie, et al.Frequent mutations of chromatin remodelinggene ARID1A in ovarian clear cell carcinoma [J].Science,2010,330(6001):228-231
20. J. S. Seo, Y. S. Ju, W. C. Lee, et al.The transcriptional landscape and mutationalprofile of lung adenocarcinoma [J].Genome Res,2012,22(11):2109-2119
21. X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].Cancer Epidemiol,2012,36(3):288-293
22. Y. Gui, G. Guo, Y. Huang, et al.Frequent mutations of chromatin remodeling genes intransitional cell carcinoma of the bladder [J].Nat Genet,2011,43(9):875-878
23. A. V. Biankin, N. Waddell, K. S. Kassahn, et al.Pancreatic cancer genomes revealaberrations in axon guidance pathway genes [J].Nature,2012,491(7424):399-405
24. F. Mitelman, F. Mertens and B. Johansson.A breakpoint map of recurrentchromosomal rearrangements in human neoplasia [J].Nat Genet,1997,15SpecNo:417-474
25. B. Weissman and K. E. Knudsen.Hijacking the chromatin remodeling machinery:impact of SWI/SNF perturbations in cancer [J]. Cancer Res,2009,69(21):8223-8230
26. C. Guichard, G. Amaddeo, S. Imbeaud, et al.Integrated analysis of somatic mutationsand focal copy-number changes identifies key genes and pathways in hepatocellularcarcinoma [J].Nat Genet,2012,44(6):694-698
27. A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
1. D. Reisman, S. Glaros and E. A. Thompson.The SWI/SNF complex and cancer[J].Oncogene,2009,28(14):1653-1668
2. B. G. Wilson and C. W. Roberts.SWI/SNF nucleosome remodellers and cancer [J].NatRev Cancer,2011,11(7):481-492
3. F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
4. N. G. Nagl, Jr., A. Patsialou, D. S. Haines, et al.The p270(ARID1A/SMARCF1)subunit of mammalian SWI/SNF-related complexes is essential for normal cell cyclearrest [J].Cancer Res,2005,65(20):9236-9244
5. Bruix J,Sherman M.Management of hepatocellular carcinoma: an update. Hepatology.2011.53(3):1020-2.
6. C. L. Peterson and I. Herskowitz.Characterization of the yeast SWI1, SWI2, and SWI3genes, which encode a global activator of transcription [J].Cell,1992,68(3):573-583
7. O. I. Kulaeva, D. A. Gaykalova and V. M. Studitsky.Transcription through chromatinby RNA polymerase II: histone displacement and exchange [J].MutatRes,2007,618(1-2):116-129
8. D. J. Tremethick.Higher-order structures of chromatin: the elusive30nm fiber[J].Cell,2007,128(4):651-654
9. N. G. Nagl, Jr., A. Patsialou, D. S. Haines, et al.The p270(ARID1A/SMARCF1)subunit of mammalian SWI/SNF-related complexes is essential for normal cell cyclearrest [J].Cancer Res,2005,65(20):9236-9244
10. X.Wang, N.G.Nagl, Jr., S. Flowers, et al.Expression of p270(ARID1A), a componentof human SWI/SNF complexes, in human tumors [J].Int J Cancer,2004,112(4):636
11. W.Wang,T.Chi,Y.Xue,etal. Architectural DNA binding by ahigh-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes[J].Proc Natl Acad Sci U S A,1998,95(2):492-498
12. J. I. Wu, J. Lessard and G. R. Crabtree.Understanding the words of chromatinregulation [J].Cell,2009,136(2):200-206
13. X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].CancerEpidemiol,2012,36(3):288-293
14. D. D. Wang, Y. B. Chen, K. Pan, et al.Decreased expression of the ARID1A gene isassociated with poor prognosis in primary gastric cancer [J].PLoSOne,2012,7(7):e40364
15. C. Guichard, G. Amaddeo, S. Imbeaud, et al.Integrated analysis of somatic mutationsand focal copy-number changes identifies key genes and pathways in hepatocellularcarcinoma [J].Nat Genet,2012,44(6):694-698
16. A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
1F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
2P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
3A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
4Kononen,J.,et al.,Tissue microarrays for high-throughput molecular Profiling of tumorspecimens.Nat Med,1998.4(7):p.844-7.
5Gao, Q., et al.,Intraturnoral balance of regulatory and cytotoxic T cells is Associatedwith Prognosis of hepatocellular carcinoma after resection. J Clin Oncol,2007.25(18):P.2586-93
6S. Jones, T. L. Wang, M. Shih Ie, et al.Frequent mutations of chromatin remodelinggene ARID1A in ovarian clear cell carcinoma [J].Science,2010,330(6001):228-231
7Z. J. Zang, I. Cutcutache, S. L. Poon, et al.Exome sequencing of gastricadenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatinremodeling genes [J].Nat Genet,2012,44(5):570-574
8D. J. Birnbaum, J. Adelaide, E. Mamessier, et al.Genome profiling of pancreaticadenocarcinoma [J].Genes Chromosomes Cancer,2011,50(6):456-465
9X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].CancerEpidemiol,2012,36(3):288-293
10J.S. Seo, Y. S. Ju, W. C. Lee, et al.The transcriptional landscape and mutational profileof lung adenocarcinoma [J].Genome Res,2012,22(11):2109-2119
11X. Wang, N. G. Nagl, Jr., S. Flowers, et al.Expression of p270(ARID1A), acomponent of human SWI/SNF complexes, in human tumors [J].Int JCancer,2004,112(4):636
12T. Takeuchi, S. Nicole, A. Misaki, et al.Expression of SMARCF1, a truncated form ofSWI1, in neuroblastoma [J].Am J Pathol,2001,158(2):663-672
13N. Cancer Genome Atlas.Comprehensive molecular characterization of human colonand rectal cancer [J].Nature,2012,487(7407):330-337
1. Ghassan Allo, Marcus Q Bernardini ARID1Aloss correlates with mismatch repairdeficiency and intact p53expression in high-grade endometrial carcinomas [J] ModernPathology(2013),1–7
2. Tsui-Lien Mao, Ie-Ming Shih. The roles of ARID1A in gynecologic cancer.[J] JGynecol Oncol.2013.24（4）：376
3. S. Yamamoto, H. Tsuda, M. Takano, et al.Loss of ARID1A protein expression occursas an early event in ovarian clear-cell carcinoma development and frequently coexistswith PIK3CA mutations [J].Mod Pathol,2012,25(4):615-624
4. K. Wang, J. Kan, S. T. Yuen, et al.Exome sequencing identifies frequent mutation ofARID1A in molecular subtypes of gastric cancer [J].Nat Genet,2011,43(12):1219-1223
5. Hollander MC, Blumenthal GM, Dennis PA.2011. PTEN loss in the continuum ofcommon cancers, rare syndromes and mouse models.[J] Nat Rev Cancer11:289–301
6. Han Liang,1,9,11Lydia W.T. Cheung, Whole-exome sequencing combined withfunctional genomics reveals novel candidate driver cancer genes in endometrial cancer,[J].Genome Res.201222:2120-2129
7. Bin Guan, Tian-Li Wang, Ie-Ming Shih.ARID1A, a Factor That Promotes Formationof SWI/SNFMediated Chromatin Remodeling, Is a Tumor Suppressor in GynecologicCancers.[J].American Association for Cancer Research.2011;DOI:10.1158/0008-5472
8. Devita VT, Hellman S, Rosenberg SA. Cancer: Principies and practice of oncology.5th eds. Philadelphia:[J] Lippincott-Raven Publishers.1997,79-102.
9. Wong CW, Lee A, Shientag L. Apoptosis: an early event in metastatic inefficiency.[J].Cancer Research.2001,61(1):333-338.
10. Li SY, Yu B, An P, et al. Influence of FasL gene expression on hepatic metastasis ofcolorectal carcinoma.[J]. Hepa Panc D Int.2004,3(2):226-229.
11. Bernstorff WV, Glick MJ, Odze RD, et al. Fas(CD95/APO-1) and Fas ligandexpression in normal pancreas and pancreatic tumors. Implications for immuneprivilege and immune escape.[J].Cancer.2002,94(10):2552-2560.
12. Shen WH, Balajee AS, Wang J. Essential role for nuclear PTEN in maintainingchromosomal integrity.[J].Mol Cell,2007,128(1):157-170．
13. Baker SJ. PTEN enters the nuclear age.[J].Mol Cell,2007,128(1)：25-28．
14. Tamguney T, Stokoe D. New insight into PTEN．[J].Cell Science,2007,120(23)：4071-4079.
15. Planchon SM, Waite KA, Eng C. The nuclear affairs of PTEN.[J].Cell Science.2008,121:249-253．
16. Liu JL, Sheng X, Hortobaryi ZK, et a1. Nuclear PTEN-Mediated growth suppressionis independent of Akt down-regulation.[J]. MolCell Biol.2005,25(7):6211-6224.
17. Zhong H, Chiles K, Feldser D, et a1. Modulation of hypoxia-inducible factor1alphaexpression by the epidermal growth factor/phosphatidylinositol3-kinase/PTEN/AKT/FRAP path-way in human prostate cancer cells:implications for tumorangiogenesis and therapeutics.[J].Cancer Res.2000,60(6):1541-1545.
18. Hara S, Oya M, Mizuno R, et a1. Akt activation in renal cell carcinoma: Contributionof a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor.[J].Ann Oncol.2005,16(6):928-933.
19. Hamada K, Sasaki T, Koni P A, et a1. The PTEN/PI3K pathway governs normalvascular development and tumor angiogenesis.[J].Genes Dev.2005,19(17):2054-2065
20.21Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway intumor growth and angiogenesis.[J].J Clin Oncol.2005,23(5):1011-1027.
21. Marrogi AJ, Travis WD, Welsh JA, et al. Nitric oxide synthase, cyclooxygenase2, andvascular endothelial growth factor in the angiogenesis of non-small cell lungcarcinoma.[J]. Clin Can Res.2000,6(12):4739-4744.
1. P. B. Dallas, S. Pacchione, D. Wilsker, et al.The human SWI-SNF complex proteinp270is an ARID family member with non-sequence-specific DNA binding activity[J].Mol Cell Biol,2000,20(9):3137-3146
2. B. Guan, M. Gao, C. H. Wu, et al.Functional Analysis of In-frame Indel ARID1AMutations Reveals New Regulatory Mechanisms of Its Tumor Suppressor Functions[J].Neoplasia,2012,14(10):986-993
3. D. J. Birnbaum, R. Sabatier, E. Mamessier, et al.[An "ariditary" form of ovariancancer][J].Med Sci (Paris),2010,26(12):1040-1042
4. S. Jones, T. L. Wang, M. Shih Ie, et al.Frequent mutations of chromatin remodelinggene ARID1A in ovarian clear cell carcinoma [J].Science,2010,330(6001):228-231
5. K. Wang, J. Kan, S. T. Yuen, et al.Exome sequencing identifies frequent mutation ofARID1A in molecular subtypes of gastric cancer [J].Nat Genet,2011,43(12):1219-1223
6. J. S. Seo, Y. S. Ju, W. C. Lee, et al.The transcriptional landscape and mutationalprofile of lung adenocarcinoma [J].Genome Res,2012,22(11):2109-2119
7. X. Zhang, Y. Zhang, Y. Yang, et al.Frequent low expression of chromatin remodelinggene ARID1A in breast cancer and its clinical significance [J].CancerEpidemiol,2012,36(3):288-293
8. A. V. Biankin, N. Waddell, K. S. Kassahn, et al.Pancreatic cancer genomes revealaberrations in axon guidance pathway genes [J].Nature,2012,491(7424):399-405
9. Y. Gui, G. Guo, Y. Huang, et al.Frequent mutations of chromatin remodeling genesin transitional cell carcinoma of the bladder [J].Nat Genet,2011,43(9):875-878
10. F. Mertens, B. Johansson, M. Hoglund, et al.Chromosomal imbalance maps ofmalignant solid tumors: a cytogenetic survey of3185neoplasms [J].CancerRes,1997,57(13):2765-2780
11. F. Mitelman, F. Mertens and B. Johansson.A breakpoint map of recurrentchromosomal rearrangements in human neoplasia [J].Nat Genet,1997,15SpecNo:417-474
12. B. Weissman and K. E. Knudsen.Hijacking the chromatin remodeling machinery:impact of SWI/SNF perturbations in cancer [J].Cancer Res,2009,69(21):8223-8230
13. C. L. Peterson and I. Herskowitz.Characterization of the yeast SWI1, SWI2, and SWI3genes, which encode a global activator of transcription [J].Cell,1992,68(3):573-583
14. Z. Kozmik, O. Machon, J. Kralova, et al.Characterization of mammalian orthologuesof the Drosophila osa gene: cDNA cloning, expression, chromosomal localization, anddirect physical interaction with Brahma chromatin-remodeling complex[J].Genomics,2001,73(2):140-148
15. C. Muchardt and M. Yaniv.ATP-dependent chromatin remodelling: SWI/SNF and Co.are on the job [J].J Mol Biol,1999,293(2):187-198
16. O. I. Kulaeva, D. A. Gaykalova and V. M. Studitsky.Transcription through chromatinby RNA polymerase II: histone displacement and exchange [J].MutatRes,2007,618(1-2):116-129
17. D. J. Tremethick.Higher-order structures of chromatin: the elusive30nm fiber[J].Cell,2007,128(4):651-654
18. A. S. Yoo and G. R. Crabtree.ATP-dependent chromatin remodeling in neuraldevelopment [J].Curr Opin Neurobiol,2009,19(2):120-126
19. N. G. Nagl, Jr., A. Patsialou, D. S. Haines, et al.The p270(ARID1A/SMARCF1)subunit of mammalian SWI/SNF-related complexes is essential for normal cell cyclearrest [J].Cancer Res,2005,65(20):9236-9244
20. Z. Nie, Y. Xue, D. Yang, et al.A specificity and targeting subunit of a humanSWI/SNF family-related chromatin-remodeling complex [J].Mol CellBiol,2000,20(23):8879-8888
21. W. Wang, T. Chi, Y. Xue, et al.Architectural DNA binding by ahigh-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes[J].Proc Natl Acad Sci U S A,1998,95(2):492-498
22. J. I. Wu, J. Lessard and G. R. Crabtree.Understanding the words of chromatinregulation [J].Cell,2009,136(2):200-206
23. D. Reisman, S. Glaros and E. A. Thompson.The SWI/SNF complex and cancer[J].Oncogene,2009,28(14):1653-1668
24. B. G. Wilson and C. W. Roberts.SWI/SNF nucleosome remodellers and cancer [J].NatRev Cancer,2011,11(7):481-492
25. X. Wang, N. G. Nagl, Jr., S. Flowers, et al.Expression of p270(ARID1A), acomponent of human SWI/SNF complexes, in human tumors [J].Int JCancer,2004,112(4):636
26. E. Crow, Z. Du and L. Li.New insights into prion biology from the novel [SWI+]system [J].Prion,2008,2(4):141-144
27.[27] X. S. Li, P. Trojer, T. Matsumura, et al.Mammalian SWI/SNF--a subunitBAF250/ARID1is an E3ubiquitin ligase that targets histone H2B [J].Mol CellBiol,2010,30(7):1673-1688
28. B. Vogelstein and K. W. Kinzler.Cancer genes and the pathways they control [J].NatMed,2004,10(8):789-799
29. S. Rodriguez-Nieto and M. Sanchez-Cespedes.BRG1and LKB1: tales of two tumorsuppressor genes on chromosome19p and lung cancer [J].Carcinogenesis,2009,30(4):547-554
30. W. J. Lowery, J. M. Schildkraut, L. Akushevich, et al.Loss of ARID1A-associatedprotein expression is a frequent event in clear cell and endometrioid ovarian cancers[J].Int J Gynecol Cancer,2012,22(1):9-14
31. E. P. Samartzis, N. Samartzis, A. Noske, et al.Loss of ARID1A/BAF250a-expressionin endometriosis: a biomarker for risk of carcinogenic transformation?[J].ModPathol,2012,25(6):885-892
32. W. Xiao, A. Awadallah and W. Xin.Loss of ARID1A/BAF250a expression in ovarianendometriosis and clear cell carcinoma [J].Int J Clin Exp Pathol,2012,5(7):642-650
33. K. C. Wiegand, S. P. Shah, O. M. Al-Agha, et al.ARID1A mutations inendometriosis-associated ovarian carcinomas [J]. N Engl J Med,2010,363(16):1532-1543
34. A. Ayhan, T. L. Mao, T. Seckin, et al.Loss of ARID1A Expression Is an EarlyMolecular Event in Tumor Progression From Ovarian Endometriotic Cyst to ClearCell and Endometrioid Carcinoma [J].Int J Gynecol Cancer,2012,22(8):1310-1315
35. H. M. Werner, A. Berg, E. Wik, et al.ARID1A loss is prevalent in endometrialhyperplasia with atypia and low-grade endometrioid carcinomas [J].Mod Pathol,2012
36. D. J. Birnbaum, D. Birnbaum and F. Bertucci.Endometriosis-associated ovariancarcinomas [J].N Engl J Med,2011,364(5):483-4; author reply484-485
37. A. Katagiri, K. Nakayama, M. T. Rahman, et al.Frequent loss of tumor suppressorARID1A protein expression in adenocarcinomas/adenosquamous carcinomas of theuterine cervix [J].Int J Gynecol Cancer,2012,22(2):208-212
38. S. Yamamoto, H. Tsuda, M. Takano, et al.Loss of ARID1A protein expression occursas an early event in ovarian clear-cell carcinoma development and frequently coexistswith PIK3CA mutations [J].Mod Pathol,2012,25(4):615-624
39. A. Katagiri, K. Nakayama, M. T. Rahman, et al.Loss of ARID1A expression is relatedto shorter progression-free survival and chemoresistance in ovarian clear cellcarcinoma [J].Mod Pathol,2012,25(2):282-288
40. Z. J. Zang, I. Cutcutache, S. L. Poon, et al.Exome sequencing of gastricadenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatinremodeling genes [J].Nat Genet,2012,44(5):570-574
41. S. Jones, M. Li, D. W. Parsons, et al.Somatic mutations in the chromatin remodelinggene ARID1A occur in several tumor types [J].Hum Mutat,2012,33(1):100-103
42. D. D. Wang, Y. B. Chen, K. Pan, et al.Decreased expression of the ARID1A gene isassociated with poor prognosis in primary gastric cancer [J].PLoS One,2012,7(7):e40364
43. D. J. Birnbaum, J. Adelaide, E. Mamessier, et al.Genome profiling of pancreaticadenocarcinoma [J].Genes Chromosomes Cancer,2011,50(6):456-465
44. A. H. Shain, C. P. Giacomini, K. Matsukuma, et al.Convergent structural alterationsdefine SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a centraltumor suppressive complex in pancreatic cancer [J].Proc Natl Acad Sci U SA,2012,109(5):E252-259
45. C. Guichard, G. Amaddeo, S. Imbeaud, et al.Integrated analysis of somatic mutationsand focal copy-number changes identifies key genes and pathways in hepatocellularcarcinoma [J].Nat Genet,2012,44(6):694-698
46. A. Fujimoto, Y. Totoki, T. Abe, et al.Whole-genome sequencing of liver cancersidentifies etiological influences on mutation patterns and recurrent mutations inchromatin regulators [J].Nat Genet,2012,44(7):760-764
47. J. Huang, Y. L. Zhao, Y. Li, et al.Genomic and functional evidence for an ARID1Atumor suppressor role [J].Genes Chromosomes Cancer,2007,46(8):745-750
48. T. Takeuchi, S. Nicole, A. Misaki, et al.Expression of SMARCF1, a truncated form ofSWI1, in neuroblastoma [J].Am J Pathol,2001,158(2):663-672
49. D. W. Serber, A. Rogala, M. Makarem, et al.The BRG1chromatin remodeler protectsagainst ovarian cysts, uterine tumors, and mammary tumors in a lineage-specificmanner [J].PLoS One,2012,7(2):e31346
50. Z. Nie, Z. Yan, E. H. Chen, et al.Novel SWI/SNF chromatin-remodeling complexescontain a mixed-lineage leukemia chromosomal translocation partner [J].Mol CellBiol,2003,23(8):2942-2952
51. L. Giulino-Roth, K. Wang, T. Y. Macdonald, et al.Targeted genomic sequencing ofpediatric Burkitt lymphoma identifies recurrent alterations in anti-apoptotic andchromatin-remodeling genes [J].Blood,2012
52. N. Cancer Genome Atlas.Comprehensive molecular characterization of human colonand rectal cancer [J].Nature,2012,487(7407):330-337
53. S. Yamamoto, H. Tsuda, M. Takano, et al.PIK3CA mutations and loss of ARID1Aprotein expression are early events in the development of cystic ovarian clear celladenocarcinoma [J].Virchows Arch,2012,460(1):77-87
54. Eleftherios P. Samartzis, Aurelia Noske, Konstantin J. Dedes.ARID1AMutations andPI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-AssociatedOvarian Carcinomas Int. J. Mol. Sci.2013,14,18824-18849