Systematic name M16932
Brief description Top 200 marker genes down-regulated in the 'proliferation' subclass of hepatocellular carcinoma (HCC); characterized by increased proliferation, high levels of serum AFP [GeneID=174], and chromosomal instability.
Full description or abstract 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 additional chromosome arms. In addition to amplifications at 11q13 in 6 of 103 tumors, 4 tumors harbored focal gains at 6p21 incorporating vascular endothelial growth factor A (VEGFA). Fluorescence in situ hybridization on an independent validation set of 210 tumors found 6p21 high-level gains in 14 tumors, as well as 2 tumors with 6p21 amplifications. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain in hepatocellular carcinomas suggested a novel, non-cell-autonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 of these tumors identified five classes, including CTNNB1, proliferation, IFN-related, a novel class defined by polysomy of chromosome 7, and an unannotated class. These class labels were further supported by molecular data; mutations in CTNNB1 were enriched in the CTNNB1 class, whereas insulin-like growth factor I receptor and RPS6 phosphorylation were enriched in the proliferation class. The enrichment of signaling pathway alterations in gene expression classes provides insights on hepatocellular carcinoma pathogenesis. Furthermore, the prevalence of VEGFA high-level gains in multiple tumor types suggests indications for clinical trials of antiangiogenic therapies.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18701503   Authors: Chiang DY,Villanueva A,Hoshida Y,Peix J,Newell P,Minguez B,LeBlanc AC,Donovan DJ,Thung SN,Solé M,Tovar V,Alsinet C,Ramos AH,Barretina J,Roayaie S,Schwartz M,Waxman S,Bruix J,Mazzaferro V,Ligon AH,Najfeld V,Friedman SL,Sellers WR,Meyerson M,Llovet JM
Exact source Table 7S: Underexpressed in Proliferation class
Related gene sets (show 9 additional gene sets from the source publication)

(show 66 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Yujin Hoshida (Broad Institute)
Source platform HUMAN_GENE_SYMBOL
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Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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