Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Genomic alterations in gastric cancers discovered via whole-exome sequencing

Authors: Jie Zhang, Weiqing Qiu, Hua Liu, Changlin Qian, Dujuan Liu, Hailong Wang, Ni Hu, Y. Tom Tang, Jianhua Sun, Zhiyong Shen

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Gastric cancer (GC) ranks the second in mortality rate among all cancers. Metastases account for most of the deaths in GC patients. Yet our understanding of GC and its metastasis mechanism is still very limited.

Methods

We performed 20 whole-exome sequencing (WES) on 5 typical metastatic gastric adenocarcinoma (GAC) patients with lymph node metastasis. We compared both the primary tumors to their metastatic lymph nodes, and a specific analysis pipeline was used to detect single nucleotide variants (SNVs), small insertions/deletions (indels) and copy number variants (CNVs).

Results

(1) We confirmed 30 candidate mutations in both primary and lymph nodes tissues, and other 7 only in primary tumors. (2) Copy number gains were observed in a large section of 17q12–21, as well as copy number losses in regions containing CDKN2A and CDKN2B in both primary and lymph nodes tissues.

Conclusions

Our results provide preliminary insights in the molecular mechanisms of GC initiation, development, and metastatic progression. These results need to be validated through large-scale studies.
Appendix
Available only for authorised users
Literature
1.
Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
Lauren P. The two histological main types of gastric carcinoma, an attempt at a histoclinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.CrossRefPubMed
3.
Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11: International Agency for Research on Cancer Web site; 2013. http://​globocan.​iarc.​fr. Accessed 24 Nov 2014
4.
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRefPubMed
5.
Zheng L, et al. Molecular basis of gastric cancer development and progression. Gastric Cancer. 2004;7(2):61–77.CrossRefPubMed
6.
7.
de Leon MP. Oncogenes and tumor suppressor genes. In: de Leon MP, editor. Familial and hereditary tumors. Springer Berlin Heidelberg; 1994. p. 35–47.CrossRef
8.
Li-Chang HH, Kasaian K, Ng Y, et al. Retrospective review using targeted deep sequencing reveals mutational differences between gastroesophageal junction and gastric carcinomas. BMC Cancer. 2015;15(1):1.CrossRef
9.
10.
Sato F, Meltzer SJ. CpG island hypermethylation in progression of esophageal and gastric cancer. Cancer. 2006;106(3):483–93.CrossRefPubMed
11.
Tamura G. Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol. 2006;12(2):192.CrossRefPubMedPubMedCentral
12.
Guo M, Yan W. Epigenetics of gastric cancer. In: Verma M, editor. Cancer Epigenetics: Risk Assessment, Diagnosis, Treatment, and Prognosis. New York: Springer; 2015. p. 783–99.
13.
Wang K, Kan J, Yuen ST, et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet. 2011;43(12):1219–23.CrossRefPubMed
14.
Wang K, Yuen ST, Xu J, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014;46(6):573–82.CrossRefPubMed
15.
Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392(6674):402–5.CrossRefPubMed
16.
Miranda E, Destro A, Malesci A, et al. Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer. Br J Cancer. 2006;95(8):1101–7.CrossRefPubMedPubMedCentral
17.
18.
19.
20.
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation. Genome Res. 2010;20(9):1297–1303.
21.
Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, Gabriel S, Meyerson M, Lander ES, Getz G. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31:213–9.CrossRefPubMedPubMedCentral
22.
23.
D'Aurizio R, Pippucci T, Tattini L, et al. Enhanced copy number variants detection from whole-exome sequencing data using EXCAVATOR2. Nucleic Acids Res. 2016;44(20):e154.PubMedPubMedCentral
24.
Thorvaldsdóttír H, et al. Integrated genomics viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14(2):178–92.CrossRefPubMed
25.
26.
Liu H, Li F, Zhu Y, et al. Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: a preliminary study. Oncotarget. 2016;7(28):43894.PubMedPubMedCentral
27.
Chen K, Yang D, Li X, et al. Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy. Proc Natl Acad Sci U S A. 2015;112(4):1107–12.CrossRefPubMedPubMedCentral
28.
Zang ZJ, Cutcutache I, Poon SL, et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 2012;44(5):570–4.CrossRefPubMed
29.
30.
31.
Liang L, Fang JY, Xu J. Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy. Oncogene. 2016;35(12):1475–82.CrossRefPubMed
32.
Katoh M, Katoh M. Evolutionary recombination hotspot around GSDML-GSDM locus is closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon. Int J Oncol. 2004;24(4):757–63.PubMed
33.
Maqani N, Belkhiri A, Moskaluk C, et al. Molecular dissection of 17q12 amplicon in upper gastrointestinal adenocarcinomas. Mol Cancer Res. 2006;4(7):449–55.CrossRefPubMed
34.
Varis A, Wolf M, Monni O, et al. Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res. 2002;62(9):2625–9.PubMed
35.
Suzuki H, Zhou X, Yin J, et al. Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers. Hum Mol Genet. 1995;4(10):1883–7.CrossRefPubMed
36.
Young RJ, Waldeck K, Martin C, et al. Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines. Pigment Cell Melanoma Res. 2014;27(4):590–600.CrossRefPubMed
Metadata
Title
Genomic alterations in gastric cancers discovered via whole-exome sequencing
Authors
Jie Zhang
Weiqing Qiu
Hua Liu
Changlin Qian
Dujuan Liu
Hailong Wang
Ni Hu
Y. Tom Tang
Jianhua Sun
Zhiyong Shen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5097-8

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project

Research article

Effect of COPD on symptoms, quality of life and prognosis in patients with advanced non-small cell lung cancer

Research article

S100A4 suppresses cancer stem cell proliferation via interaction with the IKK/NF-κB signaling pathway

Research article

The supportive care needs of women experiencing gynaecological cancer: a Western Australian cross-sectional study

Study protocol

TOPical Imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia (TOPIC-2 trial): a study protocol for a randomized controlled trial

Case report

Re-challenging immune checkpoint inhibitor in a patient with advanced non-small cell lung cancer: a case report
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits