A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population

Abstract

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.

Lynch syndrome in Mexican-Mestizo families: Genotype, phenotypes, and challenges in cascade testing among relatives at risk

“…This variant was first described by Moslein et al in 1996 [ 27 ] and it was later reported in other populations from Europe, Asia, Africa, North America, and Argentina ( Supplementary Table 1 ). It has also been reported in Mexican individuals living in the United States [ 11 ] and was found to be a recurrent variant in a previous report of LS in Mexico [ 25 ]. Fig.…”

“…Only eight studies have reported data on Mexican-Mestizo patients with molecularly confirmed LS [ 5 , 8 , [20] , [21] , [22] , [23] , [24] , [25] ] shown in Table 4 . In the present study, the MLH1 gene (67.5 %) was more frequently affected than MSH2 (22.5 %).…”

Comment on: Clinical and molecular features of pediatric cancer patients with Lynch syndrome

“…Moreover, they could have tabled the TNM staging of the tumor at the time of diagnosis similar to the study conducted by Padua et al in 2022. 3 Additionally, we feel that insight into the treatment regimens and duration of chemotherapy or immunotherapy would have augmented the quality of this paper. For instance, a 2022 study summarized the medical and surgical procedures that each of the four identified patients underwent.…”