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In the recent years, the full exome sequencing helped to reveal a  set of mutations in the genes that are not oncogenes or tumor suppressor genes by definition, but play an important role in carcinogenesis and encode proteins involved in chromatin remodeling. Among chromatin remodeling systems, which operate through the ATP-dependent mechanism, the complex SWI/ SNF attracts the great attention. The complex consists of the catalytic ATPase (SMARCA2/4), a group of conservative core subunits (SMARCB1, SMARCC1/2), and variant subunits. Abnormalities in the genes coding for each of these components have been identified as driver mutations in various human tumors. The SMARCB1 gene is of interest for practical oncogenetics, with its typical genotype-phenotype correlations. Germinal inactivating mutations (frameshift insertions/deletions, full deletions of the gene, nonsense mutations) lead to development of rhabdoid tumors in the kidneys and the brain in children in their first years of life, or even in utero. These tumors are highly malignant (Rhabdoid Tumor Predisposition Syndrome 1 – RTPS1). If a mutation carrier survives his/hers four years of life without manifestation RTPS1 with a missense mutation or has the mutation in the "hot spot" of the first or the last exon, then he/she will not develop rhabdoid tumors, but after 20 years of life, shwannomatosis may develop as multiple benign tumors of peripheral nerves. Finally, some point mutations in the exons 8–9 can result in Coffin-Siris syndrome characterized by mental retardation and developmental disorders, but no neoplasms. In this regard, rational referral of patients for direct DNA diagnostics of each of the described disease entities plays an important role, based on respective minimal criteria, as well as necessity of further development of NGS technologies (full genome and full exome sequencing) that are able to sequence not only individual exons, but all candidate genes of the disorders.

About the authors

D. S. Mikhaylenko

Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center; 51/1 3-ya Parkovaya ul., Moscow, 105425, Russian Federation

Author for correspondence.
MD, PhD, Leading Researcher, Department of Pathology Anatomy with the Molecular Genetic Group Russian Federation

M. V. Teleshova

Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev; 1 Samory Mashela ul., Moscow, 117997,
Russian Federation

MD, Research Fellow, Department of Clinical Oncology Russian Federation

G. D. Efremov

Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center; 51/1 3-ya Parkovaya ul., Moscow, 105425, Russian Federation

MD, PhD, Head of Department of Pathology Anatomy with the Molecular Genetic Group Russian Federation

B. Y. Alekseev

Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center; 51/1 3-ya Parkovaya ul., Moscow, 105425, Russian Federation

MD, PhD, Professor, Deputy Director Russian Federation


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Copyright (c) 2016 Mikhaylenko D.S., Teleshova M.V., Efremov G.D., Alekseev B.Y.

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