Molecular Profile of MSH6-Associated Colorectal Carcinomas Shows Distinct Features From Other Lynch Syndrome–Associated Colorectal Carcinomas
Noah C. Helderman, A. Lam, Diantha Terlouw, Sanne W. ten Broeke, Mar Rodríguez‐Girondo, Demi van Egmond, Alexandra M. J. Langers, Monique E. van Leerdam, Emily Rayner, Christi J. van Asperen, Liselotte P. van Hest, Hans J.P. Gille, Floor A.M. Duijkers, Anja Wagner, Ellis L. Eikenboom, Tom G.W. Letteboer, Mirjam M. de Jong, Fonnet E. Bleeker, E. Gómez, Manon Suerink, Carli M.J. Tops, Niels de Wind, Hans Morreau, Arnoud Boot, Tom van Wezel, Maartje Nielsen
Abstract
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome and is caused by pathogenic constitutional variants in 1 of the mismatch repair (MMR) genes, including MLH1, MSH2 (EPCAM), MSH6, and PMS2. Although generally referred to as 1 entity, LS exhibits a highly heterogeneous phenotype, exemplified by major differences in cancer penetrance between MMR gene variant carriers.1 These differences imply that the quality of colonoscopy, optimal surveillance intervals, treatment, preventive strategies, and other aspects of care likely differ between LS subgroups.