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

Authors
 Yoonjung Kim  ;  Mee-Yon Cho  ;  Juwon Kim  ;  Sung Nam Kim  ;  Seoung Chul Oh  ;  Kyung-A Lee 
Citation
 Oncotarget, Vol.8(41) : 69888-69905, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
Keywords
gastric cancer ; germline mutation ; molecular subtyping ; somatic mutaiton ; targeted sequencing
Abstract
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 (p= 0.548) or relapse-free survival (RFS, p=0.518). The P619fs*43 in ZBTB20 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, p.V832M) in the CDH1 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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/160942
DOI
10.18632/oncotarget.19435
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실)
Yonsei Authors
이경아(Lee, Kyung A)
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