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