Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines
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摘要
AIM To identify common copy number alterations on gastric cancer cell lines.METHODS Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis.RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.
AIM To identify common copy number alterations on gastric cancer cell lines.METHODS Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis.RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.
AIM To identify common copy number alterations on gastric cancer cell lines.METHODS Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis.RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.
引文
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2 Lauren P.The two histological main types of gastric carcinoma:diffuse and so-called intestinal-type carcinoma.An attempt at a histo-clinical classification.Acta Pathol Microbiol Scand 1965;64:31-49[PMID:14320675]
3 Burbano RR,Assump??o PP,Leal MF,Calcagno DQ,Guimar?es AC,Khayat AS,Takeno SS,Chen ES,De Arruda Cardoso Smith M.C-MYC locus amplification as metastasis predictor in intestinaltype gastric adenocarcinomas:CGH study in Brazil.Anticancer Res 2006;26:2909-2914[PMID:16886612]
4 Calcagno DQ,Leal MF,Taken SS,Assump??o PP,Demachki S,Smith Mde A,Burbano RR.Aneuploidy of chromosome 8 and C-MYC amplification in individuals from northern Brazil with gastric adenocarcinoma.Anticancer Res 2005;25:4069-4074[PMID:16309200]
5 Calcagno DQ,Guimar?es AC,Leal MF,Seabra AD,Khayat AS,Pontes TB,Assump??o PP,De Arruda Cardoso Smith M,Burbano RR.MYC insertions in diffuse-type gastric adenocarcinoma.Anticancer Res 2009;29:2479-2483[PMID:19596917]
6 Panani AD.Cytogenetic and molecular aspects of gastric cancer:clinical implications.Cancer Lett 2008;266:99-115[PMID:18381231 DOI:10.1016/j.canlet.2008.02.053]
7 Koo SH,Kwon KC,Shin SY,Jeon YM,Park JW,Kim SH,Noh SM.Genetic alterations of gastric cancer:comparative genomic hybridization and fluorescence In situ hybridization studies.Cancer Genet Cytogenet 2000;117:97-103[PMID:10704677DOI:10.1016/S0165-4608(99)00152-1]
8 Wu MS,Chang MC,Huang SP,Tseng CC,Sheu JC,Lin YW,Shun CT,Lin MT,Lin JT.Correlation of histologic subtypes and replication error phenotype with comparative genomic hybridization in gastric cancer.Genes Chromosomes Cancer 2001;30:80-86[PMID:11107179 DOI:10.1002/1098-2264(2000)9999:9999<::AID-GCC1062>3.0.CO;2-R]
9 Kimura Y,Noguchi T,Kawahara K,Kashima K,Daa T,Yokoyama S.Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization:gain of 20q and loss of18q are associated with tumor progression.Mod Pathol 2004;17:1328-1337[PMID:15154013 DOI:10.1038/modpathol.3800180]
10 Takeno SS,Leal MF,Lisboa LC,Lipay MV,Khayat AS,Assump??o PP,Burbano RR,Smith Mde A.Genomic alterations in diffuse-type gastric cancer as shown by high-resolution comparative genomic hybridization.Cancer Genet Cytogenet 2009;190:1-7[PMID:19264226 DOI:10.1016/j.cancergencyto.2008.09.007]
11 Seabra AD,Araújo TM,Mello Junior FA,Di Felipeávila Alcantara D,De Barros AP,De Assump??o PP,Montenegro RC,Guimar?es AC,Demachki S,Burbano RM,Khayat AS.Highdensity array comparative genomic hybridization detects novel copy number alterations in gastric adenocarcinoma.Anticancer Res2014;34:6405-6415[PMID:25368240]
12 Calcagno DQ,Leal MF,Seabra AD,Khayat AS,Chen ES,Demachki S,Assump??o PP,Faria MH,Rabenhorst SH,Ferreira MV,de Arruda Cardoso Smith M,Burbano RR.Interrelationship between chromosome 8 aneuploidy,C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma.World J Gastroenterol 2006;12:6207-6211[PMID:17036397 DOI:10.3748/WJG.v12.i38.6207]
13 Calcagno DQ,Freitas VM,Leal MF,de Souza CR,Demachki S,Montenegro R,Assump??o PP,Khayat AS,Smith Mde A,dos Santos AK,Burbano RR.MYC,FBXW7 and TP53 copy number variation and expression in gastric cancer.BMC Gastroenterol2013;13:141[PMID:24053468 DOI:10.1186/1471-230X-13-141]
14 de Souza CR,Leal MF,Calcagno DQ,Costa Sozinho EK,Borges Bdo N,Montenegro RC,Dos Santos AK,Dos Santos SE,Ribeiro HF,Assump??o PP,de Arruda Cardoso Smith M,Burbano RR.MYC deregulation in gastric cancer and its clinicopathological implications.PLoS One 2013;8:e64420[PMID:23717612 DOI:10.1371/journal.pone.0064420]
15 Costa Raiol LC,Figueira Silva EC,Mendes da Fonseca D,Leal MF,Guimar?es AC,Calcagno DQ,Khayat AS,Assump??o PP,de Arruda Cardoso Smith M,Burbano RR.Interrelationship between MYC gene numerical aberrations and protein expression in individuals from northern Brazil with early gastric adenocarcinoma.Cancer Genet Cytogenet 2008;181:31-35[PMID:18262050 DOI:10.1016/j.cancergencyto.2007.10.011]
16 Liang L,Fang JY,Xu J.Gastric cancer and gene copy number variation:emerging cancer drivers for targeted therapy.Oncogene2016;35:1475-1482[PMID:26073079]
17 Leal MF,Martins do Nascimento JL,da Silva CE,Vita Lamar?o MF,Calcagno DQ,Khayat AS,Assump??o PP,Cabral IR,de Arruda Cardoso Smith M,Burbano RR.Establishment and conventional cytogenetic characterization of three gastric cancer cell lines.Cancer Genet Cytogenet 2009;195:85-91[PMID:19837275 DOI:10.1016/j.cancergencyto.2009.04.020]
18 Leal MF,Calcagno DQ,Borges da Costa Jde F,Silva TC,Khayat AS,Chen ES,Assump??o PP,de Arruda Cardoso Smith M,Burbano RR.MYC,TP53,and chromosome 17 copy-number alterations in multiple gastric cancer cell lines and in their parental primary tumors.J Biomed Biotechnol 2011;2011:631268[PMID:21528007 DOI:10.1155/2011/631268]
19 Ribeiro HF,Alcantara DF,Matos LA,Sousa JM,Leal MF,Smith MA,Burbano RR,Bahia MO.Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100,a new Brazilian gastric cancer cell line.Braz J Med Biol Res 2010;43:717-721[PMID:20658094 DOI:10.1590/S0100-879X2010007500068]
20 Lima EM,Rissino JD,Harada ML,Assump??o PP,Demachki S,Guimar?es AC,Casartelli C,Smith MA,Burbano RR.Conventional cytogenetic characterization of a new cell line,ACP01,established from a primary human gastric tumor.Braz J Med Biol Res 2004;37:1831-1838[PMID:15558189 DOI:/S0100-879X2004001200008]
21 Batista dos Santos SE,Rodrigues JD,Ribeiro-dos-Santos AK,Zago MA.Differential contribution of indigenous men and women to the formation of an urban population in the Amazon region as revealed by mtD NA and Y-DNA.Am J Phys Anthropol 1999;109:175-180[PMID:10378456 DOI:10.1002/(SICI)1096-8644(199906)109]
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