Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing.

Abstract

BACKGROUND:

Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine.

METHODS:

In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data.

RESULTS:

35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e-5), differentiation (1.9e-7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database.

CONCLUSIONS:

We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.

• Authors: Hui Cai, Changqing Jing, Xusheng Chang, Dan Ding, Ting Han, Junchi Yang, Zhengmao Lu, Xuguang Hu, Zhaorui Liu, Jinshen Wang, Liang Shang, Shouxin Wu, Peng Meng, Ling Lin, Jiangman Zhao, Mingming Nie, Kai Yin
• Journal: Journal of translational medicine (J Transl Med) Vol. 17 Issue 1 Pg. 189 (06 04 2019) ISSN: 1479-5876 [Electronic] England
• PMID: 31164161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• DNA Mutational Analysis (methods)
• Female
• Gene Expression Profiling (methods)
• Genomics (methods)
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Precision Medicine
• Sequence Analysis, DNA (methods)
• Stomach Neoplasms (diagnosis, genetics, pathology, therapy)
• Young Adult