| Title | High-resolution characterization of a hepatocellular carcinoma genome. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Totoki, Y, Tatsuno, K, Yamamoto, S, Arai, Y, Hosoda, F, Ishikawa, S, Tsutsumi, S, Sonoda, K, Totsuka, H, Shirakihara, T, Sakamoto, H, Wang, L, Ojima, H, Shimada, K, Kosuge, T, Okusaka, T, Kato, K, Kusuda, J, Yoshida, T, Aburatani, H, Shibata, T |
| Journal | Nat Genet |
| Volume | 43 |
| Issue | 5 |
| Pagination | 464-9 |
| Date Published | 2011 May |
| ISSN | 1546-1718 |
| Keywords | Carcinoma, Hepatocellular, Exons, Gene Rearrangement, Genes, Tumor Suppressor, Genetic Variation, Genomic Library, Genomics, Hepacivirus, Humans, INDEL Mutation, Liver Neoplasms, Mutation, Oncogenes, Polymorphism, Single Nucleotide, Selection, Genetic |
| Abstract | Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.
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| DOI | 10.1038/ng.804 |
| Alternate Journal | Nat Genet |
| PubMed ID | 21499249 |