Pms2 is one of the four susceptibility genes in Lynch syndrome (LS), a common cancer syndrome [3]. It is involved in the DNA mismatch repair (MMR) pathway, which is crucial for maintaining genomic integrity. In humans, a mutation in Pms2, like in other MMR genes (MLH1, MSH2, MSH6), can result in LS, an autosomal-dominant condition predisposing to malignancies such as colorectal, endometrial, ovarian, and gastric cancers [4].

Heterozygous germline PMS2 variants are responsible for about 5% of LS, though their prevalence may be underestimated due to pseudogene-related screening complications [1]. In a study of French patients, 200 PMS2 heterozygous variants were identified, with 112 unique ones classified as class-3/4/5, and genomic rearrangements accounting for 18% of alterations [1]. Among class-4/5 variant carriers, the median age at first tumour onset was 49 years, with a predominance of colorectal (80%) and endometrial (8.1%) cancers [1]. PMS2 mutations contribute significantly to LS, but the penetrance for monoallelic mutation carriers seems lower than that for other MMR genes [2]. Also, PMS2 knockdown cells with reduced PMS2 expression levels show significantly reduced MMR efficiency [3].

In conclusion, Pms2 is essential for the DNA mismatch repair pathway, and its mutations are associated with Lynch syndrome. Research on Pms2-related mutations helps in understanding the molecular mechanisms of LS, and provides insights for genetic counseling and cancer surveillance for patients with Pms2-related mutations [1,2].