Abstract

Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel. Mutations were detected most frequently in the CDH1 (13/47) and TP53 (12/47) genes. As expected, somatic CDH1 mutations were positively correlated with distant metastases (p = 0.019) and tumours with signet ring cells (p = 0.043). These findings confirm the association of the CDH1 mutations with diffuse GC type. TP53 mutations were found to be significantly associated with a decrease in overall survival in patients with Lauren diffuse-type tumours (p = 0.0085), T3-T4 tumours (p = 0.037), and stage III-IV tumours (p = 0.013). Our results confirm that the detection of mutations in the main driver genes may have a significant prognostic value for GC patients and provide an independent GC-related set of clinical and molecular genetic data.

Details

Title
Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing
Author
Nemtsova, Marina V 1 ; Kalinkin, Alexey I 2 ; Kuznetsova, Ekaterina B 1 ; Bure, Irina V 3 ; Alekseeva, Ekaterina A 1 ; Bykov, Igor I 4 ; Khorobrykh, Tatiana V 4 ; Mikhaylenko, Dmitry S 5 ; Tanas, Alexander S 2 ; Kutsev, Sergey I 2 ; Zaletaev, Dmitry V 1 ; Strelnikov, Vladimir V 2   VIAFID ORCID Logo 

1  I.M. Sechenov First Moscow State Medical University, Medical Genetics Laboratory, Moscow, Russian Federation (GRID:grid.448878.f) (ISNI:0000 0001 2288 8774) ; Research Centre for Medical Genetics, Epigenetics Laboratory, Moscow, Russian Federation (GRID:grid.415876.9) 
2  Research Centre for Medical Genetics, Epigenetics Laboratory, Moscow, Russian Federation (GRID:grid.415876.9) 
3  I.M. Sechenov First Moscow State Medical University, Medical Genetics Laboratory, Moscow, Russian Federation (GRID:grid.448878.f) (ISNI:0000 0001 2288 8774) 
4  I.M. Sechenov First Moscow State Medical University, Department No. 1, Medical Faculty, Faculty Surgery, Moscow, Russian Federation (GRID:grid.448878.f) (ISNI:0000 0001 2288 8774) 
5  I.M. Sechenov First Moscow State Medical University, Medical Genetics Laboratory, Moscow, Russian Federation (GRID:grid.448878.f) (ISNI:0000 0001 2288 8774) ; Research Centre for Medical Genetics, Epigenetics Laboratory, Moscow, Russian Federation (GRID:grid.415876.9) ; N.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiologiсal Center, Moscow, Russian Federation (GRID:grid.415876.9) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-57544-3
ProQuest document ID
2342388290
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.