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Targeted and exome sequencing identified somatic mutations in hepatocellular carcinoma
Author(s) -
Hirotsu Yosuke,
Zheng TangHui,
Amemiya Kenji,
Mochizuki Hitoshi,
Guleng Bayasi,
Omata Masao
Publication year - 2016
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12663
Subject(s) - exome sequencing , exome , hepatocellular carcinoma , biology , somatic cell , wnt signaling pathway , mutation , cancer research , deep sequencing , genetics , germline mutation , dna sequencing , gene , genome
Aim Genetic analysis has revealed a subset of recurrently mutated genes and aberrant cellular signaling pathways in hepatocellular carcinoma. To investigate genetic alterations and dysregulated pathways in hepatocellular carcinoma, we performed targeted sequencing and exome analysis using next‐generation sequencer. Methods We analyzed the somatic mutational profiles of 16 genes in primary hepatocellular carcinoma by targeted ultra‐deep sequencing using nine pairs of specimens (tumor and peripheral blood) and whole‐exome sequencing using one pair of samples. Results Overall, somatic mutations with high allele fraction were identified in tumor tissues by targeted deep sequencing. Somatic mutations with high allele fraction were observed in TP53 (3/9; 33%) and CTNNB1 (2/9; 22%) genes in five out of nine (55%) specimens. In vitro analysis showed that CTNNB1 H36P mutant protein identified in tumor samples was resistant to protein degradation and promoted cell proliferation. Exome sequencing identified SLIT3 mutation, implying that dysregulation of axon guidance genes is involved in the development of hepatocellular carcinoma. These results showed that TP53 and WNT/β‐catenin signaling pathways were commonly mutated in hepatocellular carcinoma. Conclusion These results suggest that targeted sequencing and exome sequencing enable the identification of putative oncogenic driver mutations during the development of hepatocarcinoma.