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pISSN 2950-9114 eISSN 2950-9122
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Original Article

Lab Med Qual Assur 2023; 45(2): 70-75

Published online June 30, 2023


Copyright © Korean Association of External Quality Assessment Service.

Diagnostic Effectiveness of Copy Number Variation Detection Using Multiplex Ligation-Dependent Probe Amplification in Patients with Lynch Syndrome-Related Cancer

Do-Hoon Kim

Department of Diagnostic Laboratory Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea

Correspondence to:Do-Hoon Kim
Department of Diagnostic Laboratory Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea
Tel +82-53-258-7941
E-mail kdh@dsmc.or.kr

Received: February 28, 2023; Revised: March 10, 2023; Accepted: March 13, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in one of the DNA mismatch repair (MMR) genes such as mutL homologue 1 (MLH1), mutS homologue 2 (MSH2), MSH6, and postmeiotic segregation increased 2. Most pathogenic variants of LS are single nucleotide polymorphisms, but copy number variations (CNV) account for a significant proportion. Therefore, we investigated the efficacy of multiplex ligation-dependent probe amplification (MLPA) using a hereditary cancer next-generation sequencing (NGS) panel and MLPA of MMR genes in patients with LS-related cancer.
Methods: We performed hereditary cancer NGS of 48 genes, including MMR genes, and MLPA, including MLH1, MSH2, and MSH6, in 120 patients with LS-related cancer. The pathogenic variants detected by NGS were confirmed using Sanger sequencing.
Results: Of the 120 patients, 18 had pathogenic variants, of which the six most common were MSH2 gene variants. Of the six MSH2 mutations, three were CNVs detected by MLPA. Nonsense and frameshift mutations were found in MSH6 and MLH1, respectively, in two other patients.
Conclusions: In this study, CNVs were found at a higher rate in the pathogenic variants of MSH2 in patients with LS than in previous studies. Therefore, MLPA must be performed to detect CNVs in the diagnosis of LS.

Keywords: Lynch syndrome I, Lynch syndrome II, Hereditary nonpolyposis colorectal neoplasms, DNA copy number variations, Multiplex polymerase chain reaction, MutS homolog 2 protein

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