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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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. MAINOUTCOMEMEASURES: 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.

Original languageEnglish
Pages (from-to)793-803
Number of pages11
JournalDiseases of the colon and rectum
Volume65
Issue number6
DOIs
Publication statusPublished - 2022 Jun 1

Bibliographical note

Publisher Copyright:
© The ASCRS 2021.

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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