Genomic alterations in gastric cancers discovered via whole-exome sequencing

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

doi:10.1186/s12885-018-5097-8

Jie Zhang, Hailong Wang + Show 8 more

Open Access

https://doi.org/10.1186/s12885-018-5097-8

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Abstract

BackgroundGastric 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.MethodsWe 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.ConclusionsOur 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.

Highlights

Gastric cancer (GC) ranks the second in mortality rate among all cancers
We detected a large collection of single nucleotide polymorphism (SNP) and indels in both primary and lymph node metastatic tissues for all the five gastric adenocarcinoma (GAC) patients
All mutations reported here are within the protein coding regions, and we excluded these variations with greater than 5% frequency as reported in either the dbSNP database [22] or the ExAC database [25]

Summary

Introduction

Gastric cancer (GC) ranks the second in mortality rate among all cancers. Gastric Cancer (GC) is one of the most common cancers in the world, coming fourth and second in incidence and mortality rates, respectively [1]. The incidence and mortality rates of GC are decreasing, there are still around 700 thousand reported new cases and 500 thousand deaths per year [4]. The high mortality rate is largely due to the lack of efficient early diagnosis, tumor metastasis in the advanced stage, and a lack of GC-specific precision-class medications. It remains an urgent task to study its molecular mechanism of tumorigenesis and metastasis, so as to promote familial genetic screening, early diagnosis, and the development of effective therapeutic agents based on cancer-specific mutations and biomarkers

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