Genome Profiling of Pancreatic Adenocarcinoma
Genome Profiling of Pancreatic Adenocarcinoma
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DOI：
10.1002/gcc.20870
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发表时间：
2011-06-01
影响因子：
3.7
通讯作者：
Chaffanet, Max
中科院分区：
文献类型：
--
作者：
Birnbaum, David J.;Adelaide, Jose;Chaffanet, Max
胰腺癌是人类最具侵袭性的癌症之一。它显示了许多不同的染色体异常和突变。应用244K高分辨阵列比较基因组杂交(ACGH)技术，对39例胰腺癌细针活检标本和8株人胰腺癌细胞株的基因组变化进行了研究。通过肉眼观察和GISTIC分析，在1p、3p、4p、6、8p、9、10、11q、15q、17、18、19p、20p、21和22处观察到复发丢失，其中包括几个已知或可疑的抑癌基因，如ARHGEF10、ARID1A、CDKN2A/B、FHIT、PTEN、RB1、RUNX1-3、Smad4、STK11/LKB1、TP53和TUSC3。在三分之一的肿瘤和三个细胞系中发现了1p35-p36染色体区域的杂合性缺失。该区域在人类癌症中常见缺失，包含几个肿瘤抑制基因，包括ARID1A和RUNX3。我们在染色体臂1q、3q、5p、6p、7q、8q、12q、15q、18q、19q和20q上发现了频繁的遗传增益。在16个肿瘤中观察到扩增。获得或扩增了Akt2、CCND3、CDK4、FOXA2、GATA6、MDM2、MYC和SMURF1基因。最明显的扩增位于18q11.2，针对GATA6基因，GATA6基因在胰腺的初始分化和胰腺细胞类型分化中起主导作用。总之，我们已经确定了胰腺癌新的生物标志物和潜在的治疗靶点。(C)2011年Wiley-Liss，Inc.
Pancreatic adenocarcinoma is one of the most aggressive human cancers. It displays many different chromosomal abnormalities and mutations. By using 244 K high-resolution array-comparative genomic hybridization (aCGH) we studied the genome alterations of 39 fine-needle aspirations from pancreatic adenocarcinoma and eight human adenocarcinoma pancreatic cell lines. Using both visual inspection and GISTIC analysis, recurrent losses were observed on 1p, 3p, 4p, 6, 8p, 9, 10, 11q, 15q, 17, 18, 19p, 20p, 21, and 22 and comprised several known or suspected tumor suppressor genes such as ARHGEF10, ARID1A, CDKN2A/B, FHIT, PTEN, RB1, RUNX1-3, SMAD4, STK11/LKB1, TP53, and TUSC3. Heterozygous deletion of the 1p35-p36 chromosomal region was identified in one-third of the tumors and three of the cell lines. This region, commonly deleted in human cancers, contains several tumor suppressor genes including ARID1A and RUNX3. We identified frequent genetic gains on chromosome arms 1q, 3q, 5p, 6p, 7q, 8q, 12q, 15q, 18q, 19q, and 20q. Amplifications were observed in 16 tumors. AKT2, CCND3, CDK4, FOXA2, GATA6, MDM2, MYC, and SMURF1 genes were gained or amplified. The most obvious amplification was located at 18q11.2 and targeted the GATA6 gene, which plays a predominant role in the initial specification of the pancreas and in pancreatic cell type differentiation. In conclusion, we have identified novel biomarkers and potential therapeutic targets in pancreatic adenocarcinoma. (C) 2011 Wiley-Liss, Inc.