SPECTRUM MUTATIONS IN THE GENES OF HEREDITARY TUMOR SYNDROMES IN PANCREATIC CANCER

E.A. Kolesnikova1, N.A. Bodunova2, A.M. Danishevich2, E.S. Nikiforova1, P.A. Shatalov3, I.S. Shumskaya1, P.A. Malinina4, S.V. Gamayunov1, D.M. Kuchin5,6, N.M. Kiselev1,6, V.Е. Zagaynov1,6

1Nizhny Novgorod Regional Clinical Oncological Dispensary, Nizhniy Novgorod

2Moscow Clinical Scientific and Practical Center named after A.S. Loginov, Moscow

3National Medical Research Radiological Center, Obninsk

4City Polyclinic №7, Nizhny Novgorod

5Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko, Nizhny Novgorod

6Privolzhsky Research Medical University, Nizhny Novgorod

 Kolesnikova Elena A. ― Cand. of Sci. (Biol.), Head of the Molecular Genetic Laboratory of the Joint Pathology Department of the Nizhny Novgorod Regional Clinical Oncological Dispensary

11/1 Delovaya Str., Nizhniy Novgorod, 603163, Russian Federation, tel. +7-920-253-27-09, e-mail: shmelevael@yandex.ru, SPIN-code: 4573-0790, Author ID: 776189, Research ID (WOS): AAG-2288-2020, Author ID (Scopus): 57217136331, ORCID ID: 0000-0002-0859-4339

Abstract. Pancreatic cancer (PC) is one of the most unfavorable and fatal forms of malignant neoplasms. Most cases of PC are sporadic, but 5 to 10% of PC cases are due to hereditary predisposition. First aim of the study was to assess the prevalence of pathogenic/probably pathogenic variants of mutations in the genes of hereditary tumor syndromes in patients with prostate cancer in Nizhny Novgorod. New generation sequencing (NGS) was performed for 223 patients with morphologically verified prostate cancer who were treated in the conditions of the Nizhny Novgorod Regional Clinical Oncological Dispensary in the period from 2021 to 2022. Germinal highly penetrant mutations in the BRCA1/2 genes were found in 6 patients (3.3%) with prostate cancer, 1 of them in the BRCA1 gene and 5 in the BRCA2 gene. Various variants of pathogenic mutations in genes (ATM, FANCC, POLE, NBN, BLM, SMARCA4, MUTYH, FANCG) associated with various oncological syndromes were detected in 9 patients (23,1%). High prevalence rates of various pathogenic variants in prostate cancer, regardless of age and family oncological history, indicate the need for more thorough genetic diagnosis of this cohort of patients. Detection of germinal mutations in the genes of hereditary tumor syndromes in patients with PC will make it possible to identify groups at an increased risk of developing tumors ― relatives (asymptomatic carriers). Increased attention to healthy carriers of inherited mutations will help improve disease prevention and control.

Key words: pancreatic cancer, hereditary cancer syndromes, genetic testing, next generation sequencing.