Journal article

Elucidating the molecular basis of MSH2-deficienttumors by combined germline and somatic analysis

Gardenia M Vargas-Parra, Maribel Gonzalez-Acosta, Bryony A Thompson, Carolina Gomez, Anna Fernandez, Estela Damaso, Tirso Pons, Monika Morak, Jesus del Valle, Silvia Iglesias, Angela Velasco, Ares Solanes, Xavier Sanjuan, Natalia Padilla, Xavier de la Cruz, Alfonso Valencia, Elke Holinski-Feder, Joan Brunet, Lidia Feliubadalo, Conxi Lazaro Show all



In a proportion of patients presenting mismatch repair (MMR)-deficient tumors, no germline MMR mutations are identified, the so-called Lynch-like syndrome (LLS). Recently, MMR-deficient tumors have been associated with germline mutations in POLE and MUTYH or double somatic MMR events. Our aim was to elucidate the molecular basis of MSH2-deficient LS-suspected cases using a comprehensive analysis of colorectal cancer (CRC)-associated genes at germline and somatic level. Fifty-eight probands harboring MSH2-deficient tumors were included. Germline mutational analysis of MSH2 (including EPCAM deletions) and MSH6 was performed. Pathogenicity of MSH2 variants was assessed by RNA analysis and multi..

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University of Melbourne Researchers


Awarded by Spanish Ministry of Economy and Competitiveness

Awarded by Government of Catalonia

Awarded by Fundacion Mutua Madrilena

Awarded by RTICC MINECO Network

Awarded by Mexican National Council for Science and Technology (CONACyT)

Funding Acknowledgements

Grant sponsor: Spanish Ministry of Economy and Competitiveness; Grant numbers: SAF2012-33636 and SAF2015-68016-R; Grant sponsor: FEDER, a way to build Europe; Grant sponsor: Spanish Association Against Cancer; Grant sponsor: Government of Catalonia; Grant number: 2014SGR338; Grant sponsor: Fundacion Mutua Madrilena; Grant number: AP114252013; Grant sponsor: RTICC MINECO Network; Grant numbers: RD12/0036/0031 and RD12/0036/0008; Grant sponsor: Mexican National Council for Science and Technology (CONACyT); Grant number: 310756.