Profiling cancer-associated genetic alterations and molecular classification of cancer in Korean gastric cancer patients

• Published in: Oncotarget 2017-09, Vol.8 (41), p.69888-69905
• Main Authors: Kim, Yoonjung, Cho, Mee-Yon, Kim, Juwon, Kim, Sung Nam, Oh, Seoung Chul, Lee, Kyung-A
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.19435

Recently, the Cancer Genome Atlas (TCGA) Research Network and Asian Cancer Research Group provided a new classification of gastric cancer (GC) to aid the development of biomarkers for targeted therapy and predict prognosis. We studied associations between genetically aberrant profiles of cancer-related genes, environmental factors, and histopathological features in 107 paired gastric tumor-non-tumor tissue GC samples. 6.5% of our GC cases were classified as the EBV subtype, 17.8% as the MSI subtype, 43.0% as the CIN subtype, and 32.7% as the GS subtype. The distribution of four GC subgroups based on the TCGA and our dataset were similar. The MSI subtype showed a hyper-mutated status and the best prognosis among molecular subtype. However, molecular classification based on the four GC subtypes showed no significant survival differences in terms of overall survival ( = 0.548) or relapse-free survival (RFS, =0.518). The P619fs 43 in was limited to MSI group (n= 5/19, 26.3%), showing similar trends observed in TCGA dataset. Genetic alterations of the RTK/RAS/MAPK and PI3K/AKT/mTOR pathways were detected in 34.6% of GC cases (37 individual cases). We also found two cases with likely pathogenic variants (NM_004360.4: c. 2494 G>A, ) in the gene. Here, we classified molecular subtypes of GC according to the TCGA system and provide a critical starting point for the design of more appropriate clinical trials based on a comprehensive analysis of genetic alterations in Korean GC patients.