IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Lynch syndrome: clinical and genetic characterization associated with MLH1 gene mutation
Autor/es:
SILVINA B. NADIN; C BINIA; ANA LIA VARGAS; MARIEL A. FANELLI; ALEJANDRA MAMPEL; PAULA VALDEMOROS; CR CARRIZO
Lugar:
Mendoza
Reunión:
Simposio; II Simposio Internacional de Medicina Traslacional de la Facultad de Ciencias Médicas. Facultad de Ciencias Médicas, Universidad Nacional de Cuyo; 2019
Institución organizadora:
Facultad de Ciencias Médicas Universidad Nacional de Cuyo
Resumen:
Lynch Syndrome (LS) is the most frequent cause of hereditary non-polyposis colorectal cancer. LS etiology is associated with mutations of the DNA mismatch repair genes (MMR). MMR system corrects mismtached base pairs that greatly contributes to to maintain genome stability. The objective of our work was to analyze the clinical and molecular features of five unrelated patients with a clinical diagnosis of LS. Materials and methods: Genealogy was performed on family members of LS patients. Immunohistochemistry was also conducted on paraffin-embedded tumor tissues to evaluate the expressión of the MMR proteins: MLH1, MSH2, MSH6 and PMS2 (Ventana, Roche). The entire sequencing of MMR genes was performed by Illumina and / or AmpliseqTM. Results: All of the patients enrolled in the study suffered abdominal pain or enterorragia and family history of cancer related to LS. 4/5 patients showed no expression of the proteins MLH1 and PMS2 and 1/5 absence of PMS2. MMR genes sequencing revealed in all cases mutations in the MLH1 gene, in 3/5 cases a mutation with a reading frame correction in the exon 16 and in 2/5 cases nonsense mutations in exons 8 and 2. Conclusions: Colon adenocarcinoma was the primary tumor in all patients. The most frequent mutation found in our study was MLH1c.1890dupT (p.Asp631Ter1) in exon 16 which has been also reported in the South American population. Our preliminary data indicate that the molecular analysis of LS patients is essential to detect pathogenic mutations and helps to improve the identification of carrier families. These studies allows to adopt life-saving strategies for cancer prevention, early detection and treatment.