SOMATIC AND GERMLINE MUTATIONS IN GASTRIC CANCER

DOI: https://doi.org/None

M.V. Nemtsova (1,2), A.S. Tanas (1,3), E.A. Alekseeva (1,3), I.I. Bykov (1), D.V. Zaletayev (1,3), T.V. Khorobrykh (1), V.V. Strelnikov (3,4) 1 -I.M. Sechenov First Moscow State Medical University, Trubetskaya St., 8, Moscow, 119991, Russian Federation; 2 -Russian Medical Academy of Postgraduate Education, Barricadnay St. 2/1, Moscow, 123995, Russian Federation; 3 -Research Centre for Medical Genetics, Moskvorechie St, 1, Moscow, 115478, Russian Federation; 4 -Pirogov Russian National Research Medical University, Ostrovityanova St, 1, Moscow, 117997, Russian Federation

Introduction. Most cases of gastric cancer (GC) occur sporadically. Until recently, diffuse hereditary gastric cancer associated with the CDH1 gene mutations was considered the only hereditary form (about 1–3% of all tumors of the stomach). However, a significant number of familial cases without mutations in CDH1 suggests the existence of genetic mutations in other genes, which explains the familial accumulation. We propose a strategy for the mutation search in the tumor sample by use of NGS. To determine the germinal or somatic status of the identified mutations we perform their subsequent verification in normal tissue. The aim of the study. The application of NGS to identify new genetic mutations that determine the development of gastric cancer in patients. Methods. NGS, Sanger sequencing. Results. We have studied mutational profile of 50 genes associated with cancer in 10 tumor samples. Mutations and polymorphisms were identified in 12 genes. Five germline mutations, in APC (c.T3866A: p.I1289K), CDKN2B (c.G256A: p.D86N), RB1 (c.C2056A: p.H686N), MET (c.C2908T: p.R970C), ATM (c.T2572C: p.F858L), were verified and three of them were found in one patient. Conclusion. The identified mutations may have a direct bearing on the development of gastric cancer in a patient and his family and lead to the increased risk of tumor recurrence.
Keywords: 
next generation sequencing, gastric cancer, germline and somatic mutations
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