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http://hdl.handle.net/2445/171747
Title: | Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals |
Author: | 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) |
Keywords: | Càncer colorectal Genètica Colorectal cancer Genetics |
Issue Date: | 1-Jul-2020 |
Publisher: | MDPI |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/cancers12071799 |
It is part of: | Cancers, 2020, vol. 12, num. 7 |
URI: | http://hdl.handle.net/2445/171747 |
Related resource: | https://doi.org/10.3390/cancers12071799 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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DamasoE.pdf | 1.83 MB | Adobe PDF | View/Open |
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