ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2018; 9(15):2678-2686. doi:10.7150/jca.25438 This issue Cite
Research Paper
Mutations in NOTCH1 and nucleotide excision repair genes are correlated with prognosis of hepatitis B virus-associated hepatocellular carcinoma
1. Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung Molecular Medicine Research Center, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan
2. Department of Otolaryngology, Chang Gung Memorial Hospital, Linkou, 5 Fu-Hsing Street, Kweishan, Taoyuan 333, Taiwan
3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
4. Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan
5. Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan
6. Institute of Bioinformatics and Systems Biology, National Chiao Tung University, 1001 University Road, Hsinchu 300, Taiwan
7. Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, 5 Fu-Hsing Street, Kweishan, Taoyuan 333, Taiwan
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality because of its poor prognosis. Therefore, identifying targetable genetic mutations and mutational signatures associated with prognosis and treatment strategies are needed. Ultra-deep sequencing of 409 cancer genes using formalin-fixed paraffin-embedded tissue from 33 male patients with hepatitis B virus-associated HCC was performed to identify mutational signatures associated with the prognosis of HCC. A total of 47 genes were found to be mutated in more than 10% of patients. Chromatin remodeling genes were overrepresented in the mutation profile. We found patient survival was associated with mutations in NOTCH1 and the nucleotide excision repair genes which have not been described previously in HCC. From the mutation profile, six patients were eligible for Sorafenib treatment. Among the remaining patients, 7 patients had mutations in genes that are targets for other cancer drugs and 16 patients had mutations in potentially targetable genes. Only one patient carried no potential drug target. We identified mutational signatures associated with the patient survival of HCC. The findings may facilitate identifying subgroups of patients with a poor prognosis as well as potential drug targets for use in personalized strategies for HCC treatment.
Keywords: hepatocellular carcinoma, hepatitis B virus, mutation, prognosis, high-throughput nucleotide sequencing
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