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Abstract
Introduction. Microsatellite instability (MSI) indicates the presence of DNA mismatch repair deficiency. Identifying MSI in tumors is crucial for selecting therapeutic approaches, since MSI-positive tumors are extremely sensitive to immune checkpoint inhibitors. Furthermore, some tumors with MSI develop as part of such hereditary condition as Lynch syndrome.
Aim. This study aimed to investigate the frequency and etiology of MSI in malignant prostate neoplasms in Russian patients.
Materials and Methods. The study group consisted of 1,201 prostate cancer (PC) cases. MSI status was determined using a PCR panel comprising 10 microsatellite markers. In 10 out of 13 MSI-positive PC cases, targeted next-generation sequencing of MLH1, MSH2, MSH6 and PMS2 genes was performed.
Results. MSI was detected in 13 out of 1,136 (1.1 %) analyzed prostate cancer samples. The majority of patients with MSI had an aggressive disease: 90 % of MSI-positive PCs were diagnosed at stage 3 or 4, and 75 % had a high Gleason score. Mutations in the MSH2 and MSH6 genes, presumably responsible for MSI, were discovered in 5 out of 10 (50 %) sequenced cases. In one case, the germline origin of the pathogenic variant was confirmed, indicating Lynch syndrome. The mutations found in tumor tissues in three additional cases had previously been reported in patients with Lynch syndrome. However, their origin could not be determined due to the lack of non-tumor DNA samples.
Conclusion. The frequency of MSI in prostate tumors is about 1 %. Approximately 10 to 40 % of MSI-positive PCs may arise as a result of hereditary predisposition to cancer in the context of Lynch syndrome.
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