Focal gains of VEGFA and molecular classification of hepatocellular carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Derek Chiang
PROVIDER: E-GEOD-9829 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Focal gains of VEGFA and molecular classification of hepatocellular carcinoma.
Chiang Derek Y DY Villanueva Augusto A Hoshida Yujin Y Peix Judit J Newell Philippa P Minguez Beatriz B LeBlanc Amanda C AC Donovan Diana J DJ Thung Swan N SN Solé Manel M Tovar Victoria V Alsinet Clara C Ramos Alex H AH Barretina Jordi J Roayaie Sasan S Schwartz Myron M Waxman Samuel S Bruix Jordi J Mazzaferro Vincenzo V Ligon Azra H AH Najfeld Vesna V Friedman Scott L SL Sellers William R WR Meyerson Matthew M Llovet Josep M JM
Cancer research 20080801 16
Hepatocellular carcinomas represent the third leading cause of cancer-related deaths worldwide. The vast majority of cases arise in the context of chronic liver injury due to hepatitis B virus or hepatitis C virus infection. To identify genetic mechanisms of hepatocarcinogenesis, we characterized copy number alterations and gene expression profiles from the same set of tumors associated with hepatitis C virus. Most tumors harbored 1q gain, 8q gain, or 8p loss, with occasional alterations in 13 a ...[more]
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Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including ‘Wnt-CTNNB1’, ‘proliferation’ and ‘interferon-related’ gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Keywords: disease state analysis 103 hepatocellular carcinomas and 95 adjacent cirrhotic, non-tumoral liver tissue were obtained at the time of surgical resection of orthotopic transplantation.
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