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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171747
Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals
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The causal mechanism for cancer predisposition in Lynch-like syndrome (LLS) remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive (epi)genetic analysis. One hundred and fifteen LLS patients harboring MMR-deficient tumors and no germline MMR mutations were included. Mutational analysis of 26 colorectal cancer (CRC)-associated genes was performed. Pathogenicity of MMR variants was assessed by splicing and multifactorial likelihood analyses. Genome-wide methylome analysis was performed by the Infinium Human Methylation 450K Bead Chip. The multigene panel analysis revealed the presence of two MMR gene truncating mutations not previously found. Of a total of 15 additional MMR variants identified, five -present in 6 unrelated individuals- were reclassified as pathogenic. In addition, 13 predicted deleterious variants in other CRC-predisposing genes were found in 12 probands. Methylome analysis detected one constitutionalMLH1epimutation, but no additional differentially methylated regions were identified in LLS compared to LS patients or cancer-free individuals. In conclusion, the use of an ad-hoc designed gene panel combined with pathogenicity assessment of variants allowed the identification of deleterious MMR mutations as well as new LLS candidate causal genes. Constitutional epimutations in non-LS-associated genes are not responsible for LLS.
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DÁMASO, Estela, GONZÁLEZ ACOSTA, María isabel, VARGAS PARRA, Gardenía maría, NAVARRO, Matilde, BALMAÑA, Judith, RAMON Y CAJAL, Teresa, TUSET, Noemí, THOMPSON, Bryony a., MARÍN, Fátima, FERNÁNDEZ, Anna, GOMEZ, Carolina, VELASCO, Àngela, SOLANES, Ares, IGLESIAS CASALS, Sílvia, URGEL, Gisela, LÓPEZ, Consol, VALLE, Jesús del, CAMPOS, Olga, SANTACANA, Maria, MATIAS-GUIU, Xavier, LÁZARO GARCÍA, Conxi, VALLE, Laura, BRUNET, Joan, PINEDA RIU, Marta, CAPELLÁ, G. (gabriel). Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals. _Cancers_. 2020. Vol. 12, núm. 7. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/171747]