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High-resolution characterization of a hepatocellular carcinoma genome.
- Source :
-
Nature genetics [Nat Genet] 2011 May; Vol. 43 (5), pp. 464-9. Date of Electronic Publication: 2011 Apr 17. - Publication Year :
- 2011
-
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.
- Subjects :
- Carcinoma, Hepatocellular virology
Exons
Gene Rearrangement
Genes, Tumor Suppressor
Genetic Variation
Genomic Library
Genomics
Hepacivirus pathogenicity
Humans
INDEL Mutation
Liver Neoplasms virology
Mutation
Oncogenes
Polymorphism, Single Nucleotide
Selection, Genetic
Carcinoma, Hepatocellular genetics
Liver Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 21499249
- Full Text :
- https://doi.org/10.1038/ng.804