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Application of Multigene Panel Testing in Patients With High Risk for Hereditary Colorectal Cancer: A Descriptive Report Focused on Genotype-Phenotype Correlation

 Ji Soo Park  ;  Jung Won Park  ;  Saeam Shin  ;  Seung-Tae Lee  ;  Sang Joon Shin  ;  Byung Soh Min  ;  Soo Jung Park  ;  Jae Jun Park  ;  Jae Hee Cheon  ;  Won Ho Kim  ;  Tae Il Kim 
 DISEASES OF THE COLON & RECTUM, Vol.65(6) : 793-803, 2022-06 
Journal Title
Issue Date
Colorectal Neoplasms* / genetics ; Cross-Sectional Studies ; Genetic Association Studies ; Humans ; Mismatch Repair Endonuclease PMS2 / genetics ; MutS Homolog 2 Protein / genetics ; Retrospective Studies
Background: The genetic test solely based on the clinical features of hereditary colorectal cancer has limitations in clinical practice.

Objective: This study aimed to analyze the results of comprehensive multigene panel tests based on clinical findings.

Design: This was a cross-sectional study based on a prospectively compiled database.

Setting: The study was conducted at a tertiary hospital.

Patients: A total of 381 patients with high risk for hereditary colorectal cancer syndromes were enrolled between March 2014 and December 2019.

Main outcome measures: The primary outcome was to describe the mutational spectrum based on genotype-phenotype concordance and discordance.

Results: Germline mutations were identified in 89 patients for polyposis hereditary colorectal cancer genes (76 in APC; 4 in PTEN; 4 in STK11; 3 in BMPR1A; 1 in POLE; 1 in POLD1), 89 patients for nonpolyposis hereditary colorectal cancer genes (41 in MLH1; 40 in MSH2; 6 in MSH6; and 2 in PMS2), and 12 patients for other cancer predisposition genes (1 in ATM; 2 in BRCA1; 1 in BRCA2; 1 in BRIP1; 1 in MLH3; 1 in NBN; 1 in PMS1; 1 in PTCH1; 1 in TP53; and 2 in monoallelic MUTYH). If we had used direct sequencing tests of 1 or 2 major genes based on phenotype, 48 (25.3%) of 190 mutations would not have been detected due to technical differences (12.1%), less frequent genotype (4.2%), unclear phenotype (3.7%), and genotype-phenotype discordance (4.7%). The genotype-phenotype discordance is probably linked to compound heterozygote, less distinctive phenotype, and insufficient information for colorectal cancer risk.

Limitations: This study included a small number of patients with insufficient follow-up duration.

Conclusions: A comprehensive multigene panel is expected to identify more genetic mutations than phenotype-based direct sequencing, with special utility for unclear phenotype or genotype-phenotype discordance. See Video Abstract at http://links.lww.com/DCR/B844.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Min, Byung Soh(민병소) ORCID logo https://orcid.org/0000-0003-0180-8565
Park, Soo Jung(박수정)
Park, Jae Jun(박재준)
Park, Jung Won(박정원)
Park, Ji Soo(박지수) ORCID logo https://orcid.org/0000-0002-0023-7740
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
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