Format

Send to

Choose Destination
Mutat Res. 2018 Oct - Dec;778:61-71. doi: 10.1016/j.mrrev.2018.08.003. Epub 2018 Aug 23.

Genetic landscape of gallbladder cancer: Global overview.

Author information

1
Division of Preventive Oncology, National Institute of Cancer Prevention and Research, Noida, India. Electronic address: rmehrotra@icmr.org.in.
2
Division of Preventive Oncology, National Institute of Cancer Prevention and Research, Noida, India.
3
Division of Molecular Oncology, National Institute of Cancer Prevention and Research, Noida, India.
4
Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
5
Department of Surgical Gastroenterology & Hepatology, GB Pant Hospital, New Delhi, India.
6
Clinical Epidemiology, Biostatics and Bioinformatics Academic Medical Center, Amsterdam, Netherlands.
7
Laboratory Oncology Unit, Rotary Cancer Center, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
8
Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Centre, USA.
9
Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Centre, USA.
10
Department of Surgery, Clinica Alemana, Santiago, Chile.
11
New India Cancer Charity Initiative, Research and Education in Cancer and Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
12
U.S. Health Attache, India & Regional Representative, South Asia, Office of Global Affairs, DHHS, New Delhi, Delhi, India.
13
Scientist F, ICMR, New Delhi, India.

Abstract

Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC), characterized by late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. So, diverse epidemiology along with etiological factors have been discussed in the current article. Present review unravels the germ line polymorphisms contributing to GBC susceptibility through candidate gene approach and GWAS. GBC is enriched with multiple mutations consisting of both passenger and driver mutations. The identification of the hotspot driver mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. Thus, this review sheds lights on both traditional low throughput methods along with high throughput NGS used to determine somatic mutations in cancer. With the advent of GWAS and high throughput sequencing methods, it is possible to comprehend the mutational landscape of this enigmatic disease. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, management of tumor heterogeneity as a therapeutic challenge has been discussed. Future goals involve liquid biopsy based research for better clinical management of the disease. Therefore, research efforts involving discovery of non- invasive markers for early stage cancer detection along with novel therapies should be directed.

KEYWORDS:

Cancer; Candidate gene; Gallbladder; Genome wide association; Germline; Mutations; Next generation sequencing; Somatic

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center