PMS2 Pathogenic Variant in Lynch Syndrome-Associated Colorectal Cancer with Polyps

Abstract

Background Lynch syndrome (LS) is an autosomal dominant condition due to the germline mutation in the mismatch repair (MMR) genes including MLH1, MSH2, MSH6, and PMS2 (post-meiotic segregation increased 2). The MMR mutation carriers have high risk for cancers. Pathogenic PMS2 variants are rarely reported in LS-associated colorectal cancer (CRC) with colorectal polyps. The aim of the study was to investigate the genetic etiology of CRC in an individual with CRC with multiple colorectal polyps and a family history of cancers. Patients and Methods The index patient was an African male affected by CRC with multiple colorectal polyps. The clinical diagnostic for LS was based on the Amsterdam II criteria and pedigree. Next-generation sequencing with inherited cancer genes panel was used to detect the pathogenic variant. Results The patient fulfilled the Amsterdam II criteria and the pedigree revealed a family history of recurrent CRC. A deleterious PMS2 germline heterozygous mutation c.2192_2196delTAACT was detected. Conclusion Our study supports the notion that LS may be associated with polyps and shows the predisposition of PMS2 heterozygous mutation in LS-associated CRC at young age.

Analyzing Colorectal Cancer at the Molecular Level through Next-generation Sequencing in Erbil City

“…4 shows that HETEROZYGOTE PMS2 is observed at the splicing site (5982995 C>T). Usually, PMS2 mutations are implicated in lynch syndrome (LS) associated colorectal cancer in approximately 8 to 15% of cases, with variable incidence rates and depending on diagnostic methods such as PCR, microsatellite instability, IHC, or DNA sequencing (Poaty et al, 2023). Heterozygous PMS2 mutations were identified in 90.16% (55/61) of cases, while homozygous PMS2 mutations were observed in 9.83% (6/61) of LS cases (Senter, et al, 2008).…”