Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 26, 2022; 10(15): 4761-4775
Published online May 26, 2022. doi: 10.12998/wjcc.v10.i15.4761
Detection of a novel panel of 24 genes with high frequencies of mutation in gastric cancer based on next-generation sequencing
Hui-Hui Zeng, Ze Yang, Ye-Bei Qiu, Shoaib Bashir, Yin Li, Meng Xu
Hui-Hui Zeng, Ye-Bei Qiu, Shoaib Bashir, Yin Li, Meng Xu, Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, Guangdong Province, China
Hui-Hui Zeng, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, China
Ze Yang, Department of Oncology, Jinan University, Guangzhou 510630, Guangdong Province, China
Author contributions: Xu M and Li Y conceived and designed this study; Zeng HH, Ze Yang, and Qiu YB were responsible for the data collection and analysis; Bashir S wrote the draft manuscript; Xu M and Li Y revised the manuscript; all authors critically reviewed the manuscript and approved the final manuscript for publication.
Supported by the Science and Technology Foundation of Guangzhou, No. 201803010059, and the Natural Science Foundation of Bengbu Medical College, No. BYKY2019129ZD.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Bengbu Medical College (No. 2021KY029).
Informed consent statement: Informed written consent was obtained from the patient, all patients signed informed consent voluntarily.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Meng Xu, MD, PhD, Full Professor, Department of Oncology, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Avenue, Guangzhou 510630, Guangdong Province, China. 641704010@qq.com
Received: December 16, 2021
Peer-review started: December 16, 2021
First decision: January 27, 2022
Revised: February 6, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: May 26, 2022
Processing time: 158 Days and 23.3 Hours
Abstract
BACKGROUND

Gastric cancer is a leading cause of cancer-related mortality worldwide. Many somatic mutations have been identified based on next-generation sequencing; they likely play a vital role in cancer treatment selection. However, next-generation sequencing has not been widely used to diagnose and treat gastric cancer in the clinic.

AIM

To test the mutant gene frequency as a guide for molecular diagnosis and personalized therapy in gastric cancer by use of next-generation sequencing.

METHODS

We constructed a panel of 24 mutant genes to detect somatic nucleotide variations and copy number variations based on a next-generation sequencing technique. Our custom panel included high-mutation frequency cancer driver and tumour suppressor genes. Mutated genes were also analyzed using the cBioPortal database. The clinical annotation of important variant mutation sites was evaluated in the ClinVar database. We searched for candidate drugs for targeted therapy and immunotherapy from the OncoKB database.

RESULTS

In our study, the top 16 frequently mutated genes were TP53(58%), ERBB2(28%), BRCA2 (23%), NF1 (19%), PIK3CA (14%), ATR (14%), MSH2 (12%), FBXW7 (12%), BMPR1A (12%), ERBB3 (11%), ATM (9%), FGFR2 (8%), MET (8%), PTEN (6%), CHD4 (6%), and KRAS (5%). TP53 is a commonly mutated gene in gastric cancer and has a similar frequency to that in the cBioPortal database. 33 gastric cancer patients (51.6%) with microsatellite stability and eight patients (12.5%) with microsatellite instability-high were investigated. Enrichment analyses demonstrated that high-frequency mutated genes had transmembrane receptor protein kinase activity. We discovered that BRCA2, PIK3CA, and FGFR2 gene mutations represent promising biomarkers in gastric cancer.

CONCLUSION

We developed a powerful panel of 24 genes with high frequencies of mutation that could detect common somatic mutations. The observed mutations provide potential targets for the clinical treatment of gastric cancer.

Keywords: Gastric cancer; Next-generation sequencing; Mutated genes; Target sites; Microsatellite instability

Core Tip: High frequencies of mutation might provide new insights for individualized and precise treatment by use of next-generation sequencing in gastric cancer patients. However, next-generation sequencing has not been widely used to diagnose and treat gastric cancer in clinical practice. Thus, this study analysed 24 powerful genes with high frequencies of mutation based on a next-generation sequencing technique.