Lab Med Online.  2018 Oct;8(4):156-166. 10.3343/lmo.2018.8.4.156.

Germline Variants in MLH1, MSH2, and MSH6 in Korean Patients with Lynch Syndrome

Affiliations
  • 1Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
  • 2Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 3Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. hckim@skku.edu
  • 4Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kimjw@skku.edu

Abstract

BACKGROUND
The phenotypic and genetic spectrum of Lynch syndrome (LS) seems to differ according to ethnicity. The aim of this study was to investigate the clinical, pathological, and genetic features of LS in a large sample of Korean patients.
METHODS
We enrolled a total of 232 patients who fulfilled the revised Bethesda criteria (81%, 232/286) from 286 individuals who underwent genetic screening for LS (MLH1, MSH2, and MSH6 sequencing) in the Samsung Medical Center in Korea from 2004 to 2015. Histopathologic findings, microsatellite instability data, and clinical information were collected.
RESULTS
We identified 61 different pathogenic or likely pathogenic variants (39 in MLH1, 20 in MSH2, and 2 in MSH6), including 4 novel variants, in 101 unrelated Korean patients (101/232, 44%). When multiple tumor manifestations in a single patient were individually considered, there were 285 cancers recorded from 232 cases. A diverse spectrum of tumors, including colorectal cancer, endometrial cancer, stomach cancer, and ovary cancer, was observed. Patients with genetic alterations were more closely associated with a family history of cancers, double primary cancers, and the development of secondary neoplasms than patients without genetic alterations (P < 0.0001, P=0.0052, and P=0.0010, respectively).
CONCLUSIONS
We report the distribution of pathogenic variants in MLH1, MSH2, and MSH6, as well as the tumor spectrum, in a large sample of Korean patients with LS. Genetic testing could be an effective stratification strategy for surveillance of LS. This study sheds light on the genetic features of Asian patients with LS.

Keyword

Korean; Lynch syndrome; Mismatch repair gene; Pathogenic variant
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