SO01: Germline mutations in MMR genes among Russian patients with Lynch syndrome

A.S. Tsukanov, V.P. Shubin, A.V. Vardanyan, D.A. Semenov, S.I. Achkasov, S.A. Frolov, V.N. Kashnikov, Y.A. Shelygin, N.I. Pospekhova

State Scientific Center of Coloproctology, Moscow, Russia


Lynch syndrome is one of the most frequent hereditary colorectal cancer syndromes. The syndrome is caused by mutation in one of the mismatch repair (MMR) genes: mainly MLH1, MSH2, MSH6. The aim of this investigation was to study frequency and spectrum of germline mutations of MMR genes among Russian patients.


Microsatellite instability was studied in tumour samples of probands who corresponded to next criteria: age ≤ 45 and/or family history of colorectal cancer. Germline mutations in MMR genes of patients with MSI-H (high level) tumours were detected by PCR, conformation-sensitive electrophoresis and Sanger sequencing.


Microsatellite instability of high level was found in 88 tumour samples. Twenty nine out of 88 patients had germline mutations in MMR genes. Fourteen mutations were found in MLH1, 12 mutations  – in MSH2, 3 mutations – in MSH6. Ten of these mutations were frameshift, 8 – nonsense, 6 – splice sites and 5 pathogenic missense mutations.


Frequency of germline mutation in MMR genes among set of Russian patients was 35.4%. The using of NGS and MLPA methods is necessary for detection mutations in other MMR genes or large rearrangements.