The complexity of screening PMS2 in DNA isolated from formalin-fixed paraffin-embedded material.

ABSTRACT: Germline variants in the DNA mismatch repair (MMR) gene PMS2 cause 1-14% of all Lynch Syndrome cancers. Correct variant analysis of PMS2 is complex due to the presence of multiple pseudogenes and the occurrence of gene conversion. The analysis complexity increases in highly fragmented DNA from formalin-fixed paraffin-embedded (FFPE) tissue. Here we describe a reliable approach to detect true PMS2 variants in fragmented DNA. A custom NGS panel designed for FFPE tissue was used targeting four MMR genes, POLE and POLD1. Amplicon design for PMS2 was based on the position of paralogous sequence variants (PSVs) that distinguish PMS2 from its pseudogenes. PMS2 variants in exons 1-11 can be correctly curated based on this information. For exons 12-15 this is less reliable as these undergo gene con

SUBMITTER: Jansen AML 

PROVIDER: S-EPMC7028990 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature