An integrative DNA sequencing and methylation panel to assess mismatch repair deficiency

Clinical testing for mismatch repair (MMR) deficiency often entails serial testing of tumour and constitutional DNA using multiple assays. To minimize cost and specimen requirements of MMR testing, we developed an integrated targeted sequencing protocol (termed MultiMMR) that tests for promoter methylation, mutations, copy number alterations, copy neutral loss-of-heterozygosity, and microsatellite instability from a single aliquot of DNA. We performed hybrid capture of DNA sequencing libraries constructed with methylated adapters on 142 samples (60 tumours and 82 constitutional samples) from 82 patients with MMR-associated colorectal, endometrial, and brain cancers as well as a synthetic DNA mix with 11 known mutations.

Source: Journal of Molecular Diagnostics - November 28, 2020 Category: Pathology Authors: Leslie E. Oldfield, Tiantian Li, Alicia Tone, Melyssa Aronson, Melissa Edwards, Spring Holter, Rene Quevedo, Emily Van de Laar, Jordan Lerner-Ellis, Aaron Pollett, Blaise Clarke, Uri Tabori, Steven Gallinger, Sarah E. Ferguson, Trevor J. Pugh Source Type: research