MUTATIONS OF THE SMARCB1 GENE IN HUMAN CANCERS

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Abstract

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.
Email: dimserg@mail.ru
MD, PhD, Leading Researcher, Department of Pathology Anatomy with the Molecular Genetic Group Россия

M. V. Teleshova

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

Email: dimserg@mail.ru
MD, Research Fellow, Department of Clinical Oncology Россия

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

Email: dimserg@mail.ru
MD, PhD, Head of Department of Pathology Anatomy with the Molecular Genetic Group Россия

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

Email: dimserg@mail.ru
MD, PhD, Professor, Deputy Director Россия

References

  1. Tan D, Lynch HT, editors. Principles of molecular diagnostics and personalized cancer medicine. Philadelphia: Lippincott Williams and Wilkins; 2013. 968 p.
  2. Михайленко ДС, Залетаев ДВ. Молекулярно-генетическая диагностика в онкоурологии. Saarbrucken: LAP Lambert Academic Publishing; 2013. 64 c.
  3. Roy DM, Walsh LA, Chan TA. Driver mutations of cancer epigenomes. Protein Cell. 2014;5(4): 265–96. doi: 10.1007/s13238-014-0031-6.
  4. Biegel JA, Busse TM, Weissman BE. SWI/ SNF chromatin remodeling complexes and cancer. Am J Med Genet C Semin Med Genet. 2014;166C(3): 350–66. doi: 10.1002/ ajmg.c.31410.
  5. Lu P, Roberts CW. The SWI/SNF tumor suppressor complex: Regulation of promoter nucleosomes and beyond. Nucleus. 2013;4(5): 374–8. doi: 10.4161/nucl.26654.
  6. Oike T, Ogiwara H, Nakano T, Yokota J, Kohno T. Inactivating mutations in SWI/SNF chromatin remodeling genes in human cancer. Jpn J Clin Oncol. 2013;43(9): 849–55. doi: 10.1093/jjco/ hyt101.
  7. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, La-timer C, Lau KW, Marshall J, McLaren S, Men-zies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011;469(7331): 539–42. doi: 10.1038/nature09639.
  8. Witkowski L, Lalonde E, Zhang J, Albrecht S, Hamel N, Cavallone L, May ST, Nicholson JC, Coleman N, Murray MJ, Tauber PF, Huntsman DG, Schönberger S, Yandell D, Hasselblatt M, Tischkowitz MD, Majewski J, Foul-kes WD. Familial rhabdoid tumour 'avant la lettre' – from pathology review to ex-ome sequencing and back again. J Pathol. 2013;231(1): 35–43. doi: 10.1002/path.4225.
  9. Negahban S, Nagel I, Soleimanpour H, Ale-davood A, Bagheri N, Paydar M, Danesh-bod K, Hasselblatt M, Gesk S, Siebert R, Daneshbod Y. Prenatal presentation of a me-tastasizing rhabdoid tumor with homozygous deletion of the SMARCB1 gene. J Clin Oncol. 2010;28(33):e688–91. doi: 10.1200/ JCO.2010.29.9735.
  10. Sredni ST, Tomita T. Rhabdoid tumor predisposition syndrome. Pediatr Dev Pathol. 2015;18(1): 49–58. doi: 10.2350/14-07-1531-MISC.1.
  11. Teplick A, Kowalski M, Biegel JA, Nichols KE. Educational paper: screening in cancer predisposition syndromes: guidelines for the general pediatrician. Eur J Pediatr. 2011;170(3): 285–94. doi: 10.1007/s00431-010-1377-2.
  12. Gigante L, Paganini I, Frontali M, Ciabattoni S, Sangiuolo FC, Papi L. Rhabdoid tumor predisposition syndrome caused by SMARCB1 constitutional deletion: prenatal detection of new case of recurrence in siblings due to gonadal mosaicism. Fam Cancer. 2016;15(1): 123–6. doi: 10.1007/s10689-015-9836-6.
  13. Bourdeaut F, Lequin D, Brugières L, Reynaud S, Dufour C, Doz F, André N, Stephan JL, Pérel Y, Oberlin O, Orbach D, Bergeron C, Rialland X, Fréneaux P, Ranchere D, Figarella-Branger D, Audry G, Puget S, Evans DG, Pinas JC, Capra V, Mosseri V, Coupier I, Gauthier-Villars M, Pier-ron G, Delattre O. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin Cancer Res. 2011;17(1): 31–8. doi: 10.1158/1078-0432.CCR-10-1795.
  14. Eaton KW, Tooke LS, Wainwright LM, Jud-kins AR, Biegel JA. Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer. 2011;56(1): 7–15. doi: 10.1002/pbc.22831.
  15. Johansson G, Andersson U, Melin B. Recent developments in brain tumor predisposing syndromes. Acta Oncol. 2016;55(4): 401–11. doi: 10.3109/0284186X.2015.1107190.
  16. Schneppenheim R, Frühwald MC, Gesk S, Has-selblatt M, Jeibmann A, Kordes U, Kreuz M, Leuschner I, Martin Subero JI, Obser T, Oyen F, Vater I, Siebert R. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet. 2010;86(2): 279–84. doi: 10.1016/j. ajhg.2010.01.013.
  17. Bartelheim K, Sumerauer D, Behrends U, Kodetova D, Kucera F, Leuschner I, Neumayer P, Oyen F, Rübe C, Siebert R, Schneppenheim R, Seeringer A, Vasovcak P, Frühwald MC. Clinical and genetic features of rhabdoid tumors of the heart registered with the Euro-pean Rhabdoid Registry (EU-RHAB). Cancer Genet. 2014;207(9): 379–83. doi: 10.1016/j.can-cergen.2014.04.005.
  18. Kim KH, Roberts CW. Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth. Cancer Genet. 2014;207(9): 365–72. doi: 10.1016/j.cancergen.2014.04.004.
  19. Margol AS, Judkins AR. Pathology and diagnosis of SMARCB1-deficient tumors. Cancer Genet. 2014;207(9): 358–64. doi: 10.1016/j.can-cergen.2014.07.004.
  20. Le Loarer F, Zhang L, Fletcher CD, Ribeiro A, Singer S, Italiano A, Neuville A, Houlier A, Chi-bon F, Coindre JM, Antonescu CR. Consistent SMARCB1 homozygous deletions in epithelioid sarcoma and in a subset of myoepithelial carcinomas can be reliably detected by FISH in archival material. Genes Chromosomes Cancer. 2014;53(6): 475–86. doi: 10.1002/ gcc.22159.
  21. Sullivan LM, Folpe AL, Pawel BR, Judkins AR, Biegel JA. Epithelioid sarcoma is associated with a high percentage of SMARCB1 deletions. Mod Pathol. 2013;26(3): 385–92. doi: 10.1038/ modpathol.2012.175.
  22. Bruggers CS, Bleyl SB, Pysher T, Barnette P, Afify Z, Walker M, Biegel JA. Clinicopathologic comparison of familial versus sporadic atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system. Pediatr Blood Cancer. 2011;56(7): 1026–31. doi: 10.1002/ pbc.22757.
  23. Bahrami A, Lee S, Caradine KD, Raimondi SC, Folpe AL. SMARCB1 deletion by a complex three-way chromosomal translocation in an extrarenal malignant rhabdoid tumor. Cancer Genet. 2014;207(9): 437–40. doi: 10.1016/j.can-cergen.2014.08.002.
  24. Smith MJ, Wallace AJ, Bowers NL, Eaton H, Ev-ans DG. SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer Genet. 2014;207(9): 373–8. doi: 10.1016/j.cancergen.2014.04.001.
  25. Wu J, Kong M, Bi Q. Identification of a novel germline SMARCB1 nonsense mutation in a family manifesting both schwannomatosis and unilateral vestibular schwannoma. J Neurooncol. 2015;125(2): 439–41. doi: 10.1007/ s11060-015-1918-7.
  26. Rousseau G, Noguchi T, Bourdon V, Sobol H, Olschwang S. SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis. BMC Neurol. 2011;11:9. doi: 10.1186/1471-2377-11-9.
  27. Asai K, Tani S, Mineharu Y, Tsurusaki Y, Imai Y, Agawa Y, Iwaki K, Matsumoto N, Sakai N. Familial schwannomatosis with a germline mutation of SMARCB1 in Japan. Brain Tumor Pathol. 2015;32(3): 216–20. doi: 10.1007/s10014-015-0213-9.
  28. Smith MJ, Wallace AJ, Bowers NL, Rustad CF, Woods CG, Leschziner GD, Ferner RE, Ev-ans DG. Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis. Neurogenetics. 2012;13(2): 141–5. doi: 10.1007/ s10048-012-0319-8.
  29. Smith MJ, Walker JA, Shen Y, Stemmer-Rachamimov A, Gusella JF, Plotkin SR. Expression of SMARCB1 (INI1) mutations in familial schwannomatosis. Hum Mol Genet. 2012;21(24): 5239–45. doi: 10.1093/hmg/ dds370.
  30. Melean G, Velasco A, Hernández-Imaz E, Rodríguez-Álvarez FJ, Martín Y, Valero A, Hernández-Chico C. RNA-based analysis of two SMARCB1 mutations associated with familial schwannomatosis with meningiomas. Neurogenetics. 2012;13(3): 267–74. doi: 10.1007/s10048-012-0335-8.
  31. Paganini I, Sestini R, Cacciatore M, Capone GL, Candita L, Paolello C, Sbaraglia M, Dei Tos AP, Rossi S, Papi L. Broadening the spectrum of SMARCB1-associated malignant tumors: a case of uterine leiomyosarcoma in a patient with schwannomatosis. Hum Pathol. 2015;46(8): 1226–31. doi: 10.1016/j. humpath.2015.04.008.
  32. Kosho T, Okamoto N, Ohashi H, Tsurusaki Y, Imai Y, Hibi-Ko Y, Kawame H, Homma T, Tanabe S, Kato M, Hiraki Y, Yamagata T, Yano S, Sakazume S, Ishii T, Nagai T, Ohta T, Niikawa N, Mizuno S, Kaname T, Naritomi K, Narumi Y, Wakui K, Fukushima Y, Miyatake S, Mizuguchi T, Saitsu H, Miyake N, Matsumoto N. Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature. Am J Med Genet A. 2013;161A(6): 1221–37. doi: 10.1002/ajmg.a.35933.
  33. Kosho T, Okamoto N; Coffin-Siris Syndrome International Collaborators. Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am J Med Genet C Semin Med Genet. 2014;166C(3): 262–75. doi: 10.1002/ajmg.c.31407.

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

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