A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.
Alejandra Padua-BrachoJosé Antonio Velázquez-AragónVerónica Fragoso-OntiverosPaulina María Nuñez-MartínezMaría de la Luz Mejía AguayoYuliana Sánchez-ContrerasMiguel Angel Ramirez-OteroMarcela Angélica De la Fuente-HernándezSilvia Vidal-MillánTalia Wegman-OstroskyAbraham Pedroza-TorresCristian Arriaga-CanonLuis Alonso Herrera-MontalvoRosa Maria Alvarez-GómezPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- public health
- end stage renal disease
- copy number
- newly diagnosed
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- single molecule
- healthcare
- young adults
- single cell
- patient reported outcomes
- bioinformatics analysis
- cancer therapy
- drug delivery
- patient reported
- circulating tumor cells
- combination therapy
- drug induced
- genetic diversity