软组织肿瘤中染色体13q片段及该区域基因状态的分子细胞遗传学分析
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摘要
软组织肿瘤形态复杂，诊断困难，生物学行为也难以预测。随着分子细胞遗传学技术的发展和应用，许多细胞遗传学异常和特异的染色体易位被发现，不仅可以帮助确定诊断，而且还可能提示预后信息。研究发现多种软组织肿瘤存在染色体13q的异常，比较常见的是13q12-14，13q21-22和13q34区域的缺失。位于13q14位点的肿瘤抑制基因Rb，以及RFP2、KCNRG和位于13q21位点的KLF5基因可能是肿瘤抑制基因，在多种肿瘤的发生、发展中起一定的作用，但具体机制尚不清楚。
胃肠道间质肿瘤(GIST，Gastrointestinal stromal tumor)是近年来才被认识的一类软组织肿瘤，但研究进展较快。目前对于GIST的诊断、治疗等已经建立起一套比较规范化的方案，但是在如何判断生物学行为和预后以及如何确定诊断等方面还存在不少问题。人们希望能从对GIST的生物学、遗传学研究中找到解决办法。有研究发现位于染色体4q12的KIT和PDGFRA发生突变导致持续活化是GIST的关键性的致瘤事件，是肿瘤发生的早期事件。另外，14q11.1-12和14q23-24，22q13.33和22q11.22的缺失比较常见，也被认为是较早期事件。有研究报道1p和13q的缺失可能在GIST进展中起一定作用，并可能作为提示预后的指标，但相关的研究并不多，具体的基因改变尚不清楚，是否存在肿瘤抑制基因还未被确定。
本实验通过自制探针，采用双色荧光原位杂交(FISH)的方法检测了分别位于13q14和13q21上的RP11-685115，RP11-352N7，RP11-505F3等3个位点在40例软组织肿瘤患者(41个肿瘤)和95例胃肠道间质肿瘤患者(100个肿瘤)中的改变情况，并且复习总结各肿瘤的临床病理资料，分析13q异常和肿瘤临床病理资料的关系。
本实验结果显示染色体不稳定性在软组织肿瘤中有一定发生率，可能与软组织肿瘤的发生有关。染色体13q的异常在不同来源的软组织肿瘤中发生率不同，
Soft tissue rumors have various histological subtypes, with different morphological architectures and prognoses. They are challenging to pathologists due to their unusual character and the difficulties in predicting outcomes. Cytogenetic abnormalities and specific translocations are found in soft tissue tumors more commonly than in any other group of solid tumors. These abnormalities not only are useful in differentiating diagnoses but also providing insights into prognosis and pathobiology. Abnormality of chromosome 13q is found in many kinds of soft tissue tumors. The most common alterations are loss of 13q12-14, 13q21-22 or 13q34. Tumor suppressor gene Rb plays an important role in development and aggression of many kinds of tumors. Gene RFP2, KCNRG in 13q14 and gene KLF5 in 13q21 are also candidates for such a course. But few researches have been done with the status of chromosome 13q or the condition of the corresponding genes in various subtypes of soft tissue tumor.
A particular subtype of soft tissue tumor, gastrointestinal stromal tumor (GIST), emerged as a distinct entity in recent years while rapid progress about its tumorigenesis and morphological variants has been achieved. Standard protocols have established for diagnose and treatment of GIST, but difficulties are still common in differentiating diagnoses and predicting biological behavior. Recently many studies have been carried out to reveal the biological and genetic underpinnings of GISTs. Constitutive activation of the KIT or PDGFRA receptor tyrosine kinase is considered as a central and early pathogenetic event in most GISTs and generally results from oncogenic mutations. Loss of 14q11.1-12, 14q23-24, 22q13.33 and 22q11.22 are also common and early event in oncogenesis of GISTs. Some researchers have found loss of 1p and 13q in GISTs and presumed they were most likely the chromosomal loci
胃肠道间质肿瘤(GIST，Gastrointestinal stromal tumor)是近年来才被认识的一类软组织肿瘤，但研究进展较快。目前对于GIST的诊断、治疗等已经建立起一套比较规范化的方案，但是在如何判断生物学行为和预后以及如何确定诊断等方面还存在不少问题。人们希望能从对GIST的生物学、遗传学研究中找到解决办法。有研究发现位于染色体4q12的KIT和PDGFRA发生突变导致持续活化是GIST的关键性的致瘤事件，是肿瘤发生的早期事件。另外，14q11.1-12和14q23-24，22q13.33和22q11.22的缺失比较常见，也被认为是较早期事件。有研究报道1p和13q的缺失可能在GIST进展中起一定作用，并可能作为提示预后的指标，但相关的研究并不多，具体的基因改变尚不清楚，是否存在肿瘤抑制基因还未被确定。
本实验通过自制探针，采用双色荧光原位杂交(FISH)的方法检测了分别位于13q14和13q21上的RP11-685115，RP11-352N7，RP11-505F3等3个位点在40例软组织肿瘤患者(41个肿瘤)和95例胃肠道间质肿瘤患者(100个肿瘤)中的改变情况，并且复习总结各肿瘤的临床病理资料，分析13q异常和肿瘤临床病理资料的关系。
本实验结果显示染色体不稳定性在软组织肿瘤中有一定发生率，可能与软组织肿瘤的发生有关。染色体13q的异常在不同来源的软组织肿瘤中发生率不同，
Soft tissue rumors have various histological subtypes, with different morphological architectures and prognoses. They are challenging to pathologists due to their unusual character and the difficulties in predicting outcomes. Cytogenetic abnormalities and specific translocations are found in soft tissue tumors more commonly than in any other group of solid tumors. These abnormalities not only are useful in differentiating diagnoses but also providing insights into prognosis and pathobiology. Abnormality of chromosome 13q is found in many kinds of soft tissue tumors. The most common alterations are loss of 13q12-14, 13q21-22 or 13q34. Tumor suppressor gene Rb plays an important role in development and aggression of many kinds of tumors. Gene RFP2, KCNRG in 13q14 and gene KLF5 in 13q21 are also candidates for such a course. But few researches have been done with the status of chromosome 13q or the condition of the corresponding genes in various subtypes of soft tissue tumor.
A particular subtype of soft tissue tumor, gastrointestinal stromal tumor (GIST), emerged as a distinct entity in recent years while rapid progress about its tumorigenesis and morphological variants has been achieved. Standard protocols have established for diagnose and treatment of GIST, but difficulties are still common in differentiating diagnoses and predicting biological behavior. Recently many studies have been carried out to reveal the biological and genetic underpinnings of GISTs. Constitutive activation of the KIT or PDGFRA receptor tyrosine kinase is considered as a central and early pathogenetic event in most GISTs and generally results from oncogenic mutations. Loss of 14q11.1-12, 14q23-24, 22q13.33 and 22q11.22 are also common and early event in oncogenesis of GISTs. Some researchers have found loss of 1p and 13q in GISTs and presumed they were most likely the chromosomal loci
引文
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