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제 6 회 한림유전체응용연구소 세미나
등록일 : 2019-12-03
Title : Tumor mutation burden can be a good biomarker for chemotherapy responsiveness and long-term survival in gastric cancer
Speaker : KYUNG HO PAK, M.D., Ph.D.
Surgery, Hallym University Dongtan Scared Heart Hospital, Korea
Date : December 3, 2019, Tuesday, 17:00 PM
Location : Fl.7th Annex 1, Hallym University Sacred Heart Hospital
한림대학교성심병원 제1별관 7층, 한림유전체응용연구소

Abstract :
BACKGROUD
High tumor mutation burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors in various cancer. However, clinical characteristics and prognostic significance of TMB have not been elucidated yet. This study aims to delineate the clinical usefulness of TMB in gastric cancer.
METHODS
36 gastric cancer patients who have underwent gastrectomy were included in this studies. All tumor and normal gastric fresh frozen tissue from them were collected. Whole exome sequencing (WES) was processed and TMB, in silico MSI (microsatellite instability), DNA polymerase gene mutation and DNA mismatch repair gene (MMR) mutation were analyzed. For chemotherapy responsiveness and long-term survival analysis, 21 patients who underwent curative gastrectomy and complete follow-up were enrolled. Fischer exact test, Mann-Whitney U test, multiple logistic regression and Kaplan-Meier test with Cox regression analysis were used for statistical analysis.
Results
All patients were divided to high TMB (TMB-H, median 20.7) and low TMB (TMB-L, median 7.7) by the median value of TMB (12.5). Almost all parameters (age, sex, smoking, alcohol, location, differentiation, tumor size, T stage, N stage, TNM stage, lympho-vascular invasion, perineural invasion, HER2 expression, neutrophil-lymphocyte ratio, chemotherapy treatment. However, TMB-H group showed better chemotherapy response (P=0.03) and lower recurrence (P=0.06). TMB-H showed longer disease-free survival (DFS) (P=0.03) and independent prognostic factor (P=0.03, HR 21.4 (1.39-329). In addition, MSI was well matched with in silico MSI genotyper and DNA polymerase gene was well correlated TMB (P<0.01).
Conclusions
TMB can be a good predictive biomarker for chemotherapy responsiveness and prognostic marker for DFS in gastric cancer patients.
validation dataset. The classification in this study would minimize the ‘uncertainty’ in clinical interpretation, and this validated multifactorial model can be used for the reliable annotation of BRCA1/2 VUSs.