Cancers, Vol. 15, Pages 4925: DNA Mismatch Repair Gene Variant Classification: Evaluating the Utility of Somatic Mutations and Mismatch Repair Deficient Colonic Crypts and Endometrial Glands

Cancers, Vol. 15, Pages 4925: DNA Mismatch Repair Gene Variant Classification: Evaluating the Utility of Somatic Mutations and Mismatch Repair Deficient Colonic Crypts and Endometrial Glands Cancers doi: 10.3390/cancers15204925 Authors: Romy Walker Khalid Mahmood Julia Como Mark Clendenning Jihoon E. Joo Peter Georgeson Sharelle Joseland Susan G. Preston Bernard J. Pope James M. Chan Rachel Austin Jasmina Bojadzieva Ainsley Campbell Emma Edwards Margaret Gleeson Annabel Goodwin Marion T. Harris Emilia Ip Judy Kirk Julia Mansour Helen Mar Fan Cassandra Nichols Nicholas Pachter Abiramy Ragunathan Allan Spigelman Rachel Susman Michael Christie Mark A. Jenkins Rish K. Pai Christophe Rosty Finlay A. Macrae Ingrid M. Winship Daniel D. Buchanan Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. Lynch syndrome specific tumor features were evaluated for their ability to support the ACMG/InSiGHT framework in classifying variants of uncertain clinical significance (VUS) in the MMR genes. Twenty-eight CRC or EC tumors from 25 VUS carriers (6xMLH1, 9xMSH2, 6xMSH6, 4xPMS2), underwent targeted tumor sequencing for the presence of microsatellite instability/MMR-deficiency (MSI-H/dMMR) status and identification of a somatic MMR mutation (second hit). Immunohistochemical testing for the presence of dMMR crypts/glands in normal ti...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research