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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.<\/jats:p>","DOI":"10.1186\/1687-4153-2013-14","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T13:31:07Z","timestamp":1382707867000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of genomic functional hotspots with copy number alteration in liver cancer"],"prefix":"10.1186","volume":"2013","author":[{"given":"Tzu-Hung","family":"Hsiao","sequence":"first","affiliation":[]},{"given":"Hung-I Harry","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Stephanie","family":"Roessler","sequence":"additional","affiliation":[]},{"given":"Xin Wei","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Yidong","family":"Chen","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,10,25]]},"reference":[{"key":"139_CR1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/ng1861","volume":"38","author":"SL Carter","year":"2006","unstructured":"Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z: A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. 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