Novel germline MSH2 mutation in lynch syndrome patient surviving multiple cancers

We present a carrier case with a novel MSH2 gene mutation that clearly demonstrates the broad extent of LS phenotypic expression and highlights several important clinical aspects. Current evidence suggests that colorectal tumors from LS patients tend to have better prognoses than their sporadic counterparts, however survival benefits for other cancers encountered in LS are unclear.In this article we describe a family with a novel protein truncating mutation of c.2388delT in the MSH2 gene, particularly focusing on one individual carrier affected with multiple primary cancers who is surviving 25 years on. Our report of multiple primary tumors occurring in the 12-25 years interval might suggest these patients do not succumb to other extracolonic cancers, provided they are regularly followed-up.Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, is genetically heterogeneous autosomal dominant disease, caused by mutations in one of at least four mismatch repair (MMR) genes, most frequently MLH1 or MSH2, which account for about 50% and 40% of cases respectively [1]. More than 1000 unique mutations were reported in each of these genes http://www.insight-group.org webcite. Truncating mutations are the most frequent cause of deficient MMR function, comprising about 68% and 82% of the types of mutations found in the MLH1 and MSH2 genes respectively [1].Clinically LS is characterized by a high risk for early-onset colorectal and endometrial cancers and also a moderate risk for urinary tract, ovarian, small bowel, stomach and biliary tract cancers. LS accounts for 2% to 5% of all colorectal cancers [2]. Recognition of LS, leading to molecular screening for MMR genes in a proband, is currently based on the clinico-familial Amsterdam II criteria and/or clinico-pathological Bethesda criteria [3]. Identification of LS causing mutations is important for clinical surveillance in carriers and genetic testing for at risk relatives.Considerable variabilit