Germline nonsense-mutations of the SMARCB1 gene in Russian patients with rhabdoid renal tumors

Efremov3; D. Yu. Kachanov2; E. V. Raykina2; V. O. Bobrynina4; S. G. Lavrina2; A. M. Mitrofanova2; D. M. Konovalov2; S. R. Varfolomeeva2; B. Ya. Alekseev3 Affiliations: 1: НИИ урологии и интервенционной радиологии им. Н.А. Лопаткина - филиал ФГБУ "НМИРЦ" Минздрава России; ФГБНУ «Медико-генетический научный центр»; Институт молекулярной медицины ФГОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России 2: ФГБУ «Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России 3: НИИ урологии и интервенционной радиологии им. Н.А. Лопаткина - филиал ФГБУ "НМИРЦ" Минздрава России 4: ЗАО «Геноаналитика» Publication date: 1 января 2017 г. Source: Onkourologiâ, Volume 13, Number 2, 2017, pp. 14-19(6) Publisher: Directory of Open Access Journals DOI: https://doi.org/10.17650/1726-9776-2017-13-2-14-19 Abstract The malignant rhabdoid tumor (RT) is one of the most aggressive childhood neoplasm. RTs are characterized by the presence of inactivating mutations in the SMARCB1 (hSNF5/INI1/BAF47) gene – a tumor suppressor localized in 22q11.2. Up to 30 % of RTs caused by germline mutations of this gene, to date those cases are considered as a manifestation of the rhabdoid tumor predisposition syndrome type 1 (RTPS1). We have analyzed the SMARCB1 mutations by polymerase chain reaction and subsequent Sanger sequencing in 18 patients with RT in different localizations for improving of genetic laboratory diagnostics of the RTPS1, as well as searching of genotype-phenotype correlations in this disease. Three patients had de novo nonsense-mutations c.157C→T (p.R53*), c.669_670del (p.C223*) and c.843G→A (p.W281*), confirming RTPS1, which were associated with RT in the kidney, early age at diagnosis (median 2.6 months) and poor prognosis. Identification of germline SMARCB1 mutations in the patients with RTs is essential to assess the risk of metachronous tumors and for genetic counseling of other family members. https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=17#134823