Deep Targeted Sequencing and Its Potential Implication for Cancer Therapy in Chinese Patients with Gastric Adenocarcinoma. (8th February 2021)

• Record Type: Journal Article
• Authors: Yu, Pengfei; Wang, Yusheng; Yu, Yanfei; Wang, Aodi; Huang, Ling; Zhang, Yuan; Liu, Wenjing; Wu, Haiyan; Yao, Ming; Du, Yi‐An; Cheng, Xiangdong
• Is Part Of: Oncologist. Volume 26:Number 5(2021)
• Page Start: e756
• Page End: e768
• Publication Date: 2021-02-08
• Subjects: Gastric adenocarcinoma -- Next‐generation sequencing -- Tumor mutational burden -- Microsatellite instability -- Microorganisms; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1002/onco.13695
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Introduction: Gastric cancer (GC) has a high incidence and mortality rate, especially in East Asians, and about 90% of GCs are adenocarcinomas. Histological and etiological heterogeneity and ethnic diversity make molecular subtyping of GC complicated, thus making it difficult to determine molecular division systems and standard treatment modalities. Limited cohorts from South Korea, Singapore, Australia, and Japan have been studied; however, the mutational landscape of gastric adenocarcinomas in Chinese patients is still unknown. Methods: We performed a targeted sequencing panel focusing on cancer‐related genes and tumor‐associated microorganisms of 529 gastric adenocarcinoma samples with matched blood controls. We identified 449 clinically relevant gene mutations. Results: Approximately 47.1% of Chinese patients with GC harbored at least one actionable mutation. The top somatic mutations were TP53, ARID1A, LRP1B, PIK3CA, ERBB2, CDH1, KRAS, FAT4, CCNE1, and KMT2D . Truncation mutations of ARID1A, KMT2D, RNF43, TGFBR2, and CIC occurred in patients with high tumor mutational burden. Gene amplifications of ERBB2, CCNE1, CDK12, and CCND1 were detected in patients with low tumor mutational burden. Pathway analysis revealed common gene alterations in the Wnt and PI3K/Akt signaling pathways. The ratio of patients with high microsatellite instability was significantly lower than other cohorts, and high microsatellite instability and Epstein‐Barr virus (EBV)–positive features seemed mutually inclusive in Chinese patients with GC. In 44 (8.3%) patients, 45 germline mutations were identified, among which SPINK1 mutations, all SPINK1 c.194 + 2T > C, were present in 15.9% (7/44) of patients. Microorganisms found in Chinese patients with GC included Helicobacter pylori, EBV, hepatitis B virus, and human papillomavirus types 16 and 18. Conclusion: Identification of varied molecular features by targeted next‐generation sequencing provides more insight into patient stratification and offers more possibilities for both targeted therapies and immunotherapies of Chinese patients with GC. Implications for Practice: This study investigated the genomic alteration profile of 529 Chinese patients with gastric adenocarcinoma by deep targeting sequencing, which might be the largest Chinese cohort on the genomic research of gastric adenocarcinoma up to now. Abstract : Novel molecular targeted therapies for gastric cancer are urgently needed. This article explores the mutational landscape covering somatic, germline, and microorganisms among a cohort of Chinese patients with gastric cancer. Findings provide insight on patient stratification and potential molecular targets, and for developing new treatment strategies for patients in China and worldwide.