Identification of genomic functional hotspots with copy number alteration in liver cancer

Abstract

Copy number alterations (CNAs) can be observed in most of cancer patients. Several oncogenes and tumor suppressor genes with CNAs have been identified in different kinds of tumor. However, the systematic survey of CNA-affected functions is still lack. By employing systems biology approaches, instead of examining individual genes, we directly identified the functional hotspots on human genome. A total of 838 hotspots on human genome with 540 enriched Gene Ontology functions were identified. Seventy-six aCGH array data of hepatocellular carcinoma (HCC) tumors were employed in this study. A total of 150 regions which putatively affected by CNAs and the encoded functions were identified. Our results indicate that two immune related hotspots had copy number alterations in most of patients. In addition, our data implied that these immune-related regions might be involved in HCC oncogenesis. Also, we identified 39 hotspots of which copy number status were associated with patient survival. Our data implied that copy number alterations of the regions may contribute in the dysregulation of the encoded functions. These results further demonstrated that our method enables researchers to survey biological functions of CNAs and to construct regulation hypothesis at pathway and functional levels.

Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer

“…The expression levels of 13 previously reported immune metagenes were calculated as the mean of the log2-transformed expression of the member genes (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). These metagenes correspond to various immune cell types and reflect various immune functions ( Supplementary Table S2).…”

“…In a pooled analysis of solid tumors in The Cancer Genome Atlas (TCGA) database, the total number of somatic mutations and the number of new antigen epitopes (i.e., neoantigen load) correlated with immune infiltration (9)(10)(11). In hepatocellular, squamous cell lung cancer, and colorectal carcinomas greater number of copy number alterations were associated with higher immunogenicity (12)(13)(14). On the basis of these observations one can hypothesize that the more genomic alterations a cancer has, the greater the immune infiltration is, due to more immunogenic neoantigens in these cancers.…”

Identification of differentially expressed molecular functions associated with breast cancer using Gibbs sampling

“…Structural molecule activity is defined as the action of a molecule that contributes to the structural integrity of a complex or assembly within or outside a cell (29). A previous study demonstrated that structural molecule activity was among the top ten gain/loss spatial functional hotspots of hepatocellular carcinoma with enriched functions (29).…”

Copy Number Networks to Guide Combinatorial Therapy of Cancer and Proliferative Disorders

“…However, the chromosome arm network highlights a problem of charting CNA interactions in cancer, namely amplifications and deletions are not distributed randomly over the genome. Rather CNAs are flanked by hot spots for DNA rearrangements and can incorporate many genes (Beroukhim et al, 2010;Hsiao et al, 2013). This poor resolution can make the identification of causative gene pairs difficult.…”