Using Somatic Mutations from Tumors to Classify Variants in Mismatch Repair Genes.

ABSTRACT: Present guidelines for classification of constitutional variants do not incorporate inferences from mutations seen in tumors, even when these are associated with a specific molecular phenotype. When somatic mutations and constitutional mutations lead to the same molecular phenotype, as for the mismatch repair genes, information from somatic mutations may enable interpretation of previously unclassified variants. To test this idea, we first estimated likelihoods that somatic variants in MLH1, MSH2, MSH6, and PMS2 drive microsatellite instability and characteristic IHC staining patterns by calculating likelihoods of high versus low normalized variant read fractions of 153 mutations known to be pathogenic versus those of 760 intronic passenger mutations from 174 paired tumor-normal samples. M

SUBMITTER: Shirts BH 

PROVIDER: S-EPMC6035155 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature