Oncotarget

Research Papers:

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

Yoonjung Kim, Mee-Yon Cho, Juwon Kim, Sung Nam Kim, Seoung Chul Oh and Kyung-A Lee _

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Oncotarget. 2017; 8:69888-69905. https://doi.org/10.18632/oncotarget.19435

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Abstract

Yoonjung Kim1, Mee-Yon Cho2, Juwon Kim3, Sung Nam Kim4, Seoung Chul Oh5 and Kyung-A Lee1

1Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea

2Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea

3Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

4Department of Pathology, Samkwang Medical Labotories, Seoul, Korea

5Department of Laboratory Medicine, Gangnam Severance Hospital, Seoul, Korea

Correspondence to:

Kyung-A Lee, email: [email protected]

Juwon Kim, email: [email protected]

Keywords: gastric cancer, molecular subtyping, germline mutation, somatic mutaiton, targeted sequencing

Received: October 26, 2016     Accepted: June 20, 2017     Published: July 22, 2017

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.


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