Targeted next generation sequencing screening of Lynch syndrome in Tunisian population

In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients ’ tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenicMSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR,POLE andPOLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected inMLH1 (n  = 5) orMSH2 (n  = 1). Two of six patients were from the same family and both were found to carry a novel in-frameMLH1 deletion, predicted to affect MLH1 function. AllMLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germlineMSH2 variant.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research