Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations. Cancer Genomics Proteomics 2017;14(6):495-506
Date
11/08/2017Pubmed ID
29109099Pubmed Central ID
PMC6070325DOI
10.21873/cgp.20059Scopus ID
2-s2.0-85046630667 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
BACKGROUND: Gallbladder carcinoma (GBC) is a subtype of biliary tract malignancy with poor prognosis and high fatality rate. The present study was designed to uncover somatic and rare germline mutations in GBC to reveal the disease biology and understand the clinical importance of mutation profile in terms of prognostics and actionability.
MATERIALS AND METHODS: We performed ultra-deep sequencing across 409 cancer-related genes in 11 GBC patients of North-Indian descent. NGS data analysis was performed using Ion Reporter and several other publicly available resources and databases.
RESULTS: We identified 184 nonsynonymous somatic and 60 rare germline mutations in bona-fide cancer drivers such as SMAD family member 4 (SMAD4), lysine methyltransferase 2C (KMT2C), and tumor protein p53 (TP53). All the early-onset cases or hypermutated cases harbored mutation(s) in critical DNA-repair genes. Additionally, we detected 9 novel genes with high-impact somatic mutations in GBC.
CONCLUSION: Our results indicated the significance of inherited rare germline mutations in DNA-repair pathway genes in addition to acquired somatic mutations in GB carcinogenesis.
Author List
Yadav S, DE Sarkar N, Kumari N, Krishnani N, Kumar A, Mittal BAuthor
Navonil De Sarkar PhD Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
FemaleGallbladder Neoplasms
Germ-Line Mutation
Humans
Male
Molecular Targeted Therapy
