Gastric cancer is a high incidence malignancy in China, but the disease is often diagnosed at an advanced stage with limited therapeutic options and poor prognosis. Unfortunately, limited progress of target and immune therapy has achieved in gastric cancer due to tumor heterogeneity and the lack of effective biomarkers in the clinical. Thus the precise understanding of gastric cancer genomic profiling is urgent for exploring clinical strategy of this malignancy.
Formalin Fixed Paraffin Embedded (FFPE) samples of 110 Chinese gastric cancer patients were collected for next-generation sequencing (NGS)-based 450 genes panel assay. Genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, gene fusions and rearrangement were assessed. Microsatellite instability (MSI) status and tumor mutational burden (TMB) were also acquired by NGS algorithm.
There were 71 males (64.6%) and 39 females (35.4%) diagnosed as gastric cancer with a median age of 62 years old. The most frequent genomic alterations in Chinese gastric cancer patients were revealed as TP53 (66.4%), ARID1A (18.2%), LRP1B (17.3%), CDH1 (15.5%), CCNE1 (14.5%), FAT4 (13.6%), ERBB2 (11.8%), SMAD4 (10.9%), KMT2D (10.9%), RNF43 (10.9%), TGFBR2 (10.0%), KRAS (10.0%), APC (10.0%). Some actionable aberrantly activated mutations were identified in genes such as FGFR1/2/3 (10.0%), BRCA1/2 (6.4%) and PI3K/mTOR pathway including FBXW7, MTOR, PIK3CA, PTEN, STK11, TSC1 and TSC2 (20.0%). In total, 39.1% of patients carried one or more actionable genomic alterations, which indicated the potential clinical benefits of targeted therapies for them. The percentage of patients with germline mutations was 9.1% in current cohort. These germline mutation genes were mainly in homologous recombination (HR) pathways such as BRCA1/2, ATM and BARD1.
In this study, 39.1% of Chinese gastric cancer patients carried actionable genomic alterations which could potentially guide and influence personalized treatments. About 9.1% patients harbored germline mutations mainly in HR pathway. All these genomic identifications in Chinese gastric cancer cohort may provide useful information on drug discovery and biomarker exploration.
Clinical trial identification
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Y. Zheng, Q. Cui, A. Wang, H. Chen, W. Shi, K. Wang, M. Yao: Employee: OrigiMed. All other authors have declared no conflicts of interest.