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

Int J Mol Sci. 2022 Sep 30;23(19):11549. doi: 10.3390/ijms231911549.


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.

Keywords: EPCAM; Lynch syndrome; MLH1; MSH2; MSH6; PMS2; mutations; pathogenic variants; variants of uncertain significance.

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • DNA Mismatch Repair / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Germ-Line Mutation
  • Humans
  • Immune Checkpoint Inhibitors
  • Mexico / epidemiology
  • MutS Homolog 2 Protein / genetics
  • Retrospective Studies


  • DNA-Binding Proteins
  • Immune Checkpoint Inhibitors
  • MutS Homolog 2 Protein