Home > A. Molecular pathology > SMARCB1


MIM.601607 - Locus 22q11.2

Monday 24 November 2003

INI1 is a ubiquitously expressed protein encoded by the hSNF/INI1 gene located on chromosome 22q.11.2. The hSNF/INI1 gene has been implicated as tumor suppressor gene in peripheral rhabdoid tumors and atypical teratoid/rhabdoid tumors (AT/RTs) of the central nervous system (CNS).

Homozygous inactivation of this gene is involved in the pathogenesis of renal and extrarenal malignant rhabdoid tumors of childhood, and immunohistochemical loss of INI1 was initially thought to be specific for this family of tumors.


Nucleosome remodeling complexes modify chromatin topology in an ATP-dependent manner by disrupting DNA-histone interactions. They thereby facilitating sliding of the nucleosome, and hence the accessibility of the DNA to transcription factors.

The SWI/SNF complex regulates genes locally, and analyses of yeast SWI/SNF mutants revealed that transcription of 5% of all yeast genes is influenced by SWI/SNF mutations.

The SWI/SNF core complex consists of SNF5/INI1, BRG1, BRM, BAF155, and BAF170. SWI/SNF interacts with many protein complexes central to cancer development, such as RB, p53, MYC, MLL, BRCA1, and beta-catenin; hence, functional inactivation of SWI/SNF impinges on a multitude of cellular growth control pathways.


- somatic or germline deletions in

  • malignant rhabdoid tumor
  • atypical teratoid and rhabdoid tumor (AT/TR)
  • brain primitive neuroectodermal tumor (cPNET)
  • epithelioid sarcoma (#19342946#)

- germline mutations in

  • malignant rhabdoid tumor syndrome (#15101046#)
  • familial schwannomatosis (#17357086#)

Expression in tumors

- central nervous tumors (AT/TR apart) (nuclear pattern)

Diagnostic immunochemistry

- loss of INI1/SNF5 expression in tumors

  • malignant rhabdoid tumors (MRT)
  • atypical teratoid and rhabdoid tumor (AT/TR) (#15105654#)
  • adult myoepithelial carcinoma
  • myoepithelial carcinoma of soft tissue of the children (41%) (#18043035#)
  • epithelioid sarcoma (90%) (#19342946#)
  • epithelioid MPNSTs

- commercial antibodies

  • monoclonal BAF47/SNF5 (INI1) antibody (clone 25, BD Transduction Labs, San Diego, CA)

- intact INI1 gene region with paradoxical loss of protein expression in AT/RT: implications for a possible novel mechanism associated with absence of INI1 protein immunoreactivity. (#22020042#)


- modulation of cell growth and actin cytoskeleton organization (#15150092#)
- control of the G1-S transition of the cell cycle (#12226744#)


- Germline mutations are found in 35% of apparently sporadic RT. (#21208904#)
- 20% of patients with germline mutation develop the disease after 2 years of age. (#21208904#)
- There is a very high proportion of germ-cell mosaicism or of de novo mutations in RPS (rhabdoid tumor predisposition syndrome). (#21208904#)
- The 2 years’ overall survival is 7% in mutated and 29% in wild-type patients, mainly due to the worse outcome of RT in younger patients. (#21208904#)
- There is a high proportion of germline mutations in patients with RT that can be found at any age and up to 60% in the youngest patients. (#21208904#)
- Genetic counseling is recommended given the low but actual risk of familial recurrence.


- Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. 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, Pierron G, Delattre O. Clin Cancer Res. 2011 Jan 1;17(1):31-8. PMID: #21208904# (Free)

- Intact INI1 Gene Region With Paradoxical Loss of Protein Expression in AT/RT: Implications for a Possible Novel Mechanism Associated With Absence of INI1 Protein Immunoreactivity. Tsai CY, Wong TT, Lee YH, Chao ME, Lin SC, Liu DJ, Liang ML, Wang HW, Ming-Tak Ho D. Am J Surg Pathol. 2011 Oct 20. PMID: #22020042#

- Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ, Koellhoffer EC, Pomeroy SL, Orkin SH, Roberts CW. Cancer Cell. 2010 Oct 19;18(4):316-28. Erratum in: Cancer Cell. 2011 Jan 18;19(1):153. PMID: #20951942# [Free]

- Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Jagani Z, Mora-Blanco EL, Sansam CG, McKenna ES, Wilson B, Chen D, Klekota J, Tamayo P, Nguyen PT, Tolstorukov M, Park PJ, Cho YJ, Hsiao K, Buonamici S, Pomeroy SL, Mesirov JP, Ruffner H, Bouwmeester T, Luchansky SJ, Murtie J, Kelleher JF, Warmuth M, Sellers WR, Roberts CW, Dorsch M. Nat Med. 2010 Dec;16(12):1429-33. PMID: #21076395#

- Oncogenesis caused by loss of the SNF5 tumor suppressor is dependent on activity of BRG1, the ATPase of the SWI/SNF chromatin remodeling complex. Wang X, Sansam CG, Thom CS, Metzger D, Evans JA, Nguyen PT, Roberts CW. Cancer Res. 2009 Oct 15;69(20):8094-101. PMID: #19789351# [Free]

- Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic instability. McKenna ES, Sansam CG, Cho YJ, Greulich H, Evans JA, Thom CS, Moreau LA, Biegel JA, Pomeroy SL, Roberts CW. Mol Cell Biol. 2008 Oct;28(20):6223-33. PMID: #18710953# [Free]

- Uterine neoplasms composed of rhabdoid cells do not exhibit loss of INI1 immunoreactivity and are not related to childhood malignant rhabdoid tumor. Al-Hussaini M, Hirschowitz L, McCluggage WG. Int J Gynecol Pathol. 2008 Apr;27(2):236-42. PMID: #18317218#

- SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma. Kohashi K, Oda Y, Yamamoto H, Tamiya S, Oshiro Y, Izumi T, Taguchi T, Tsuneyoshi M. Am J Surg Pathol. 2008 Aug;32(8):1168-74. PMID: #18580682#

- Koitabashi M, Kanazawa T, Tamura K, Tsukada S, Suzuki M, Morikawa A, Ogawa C, Hirado J. A novel mutation of the SMARCB1 gene in a case of extrarenal malignant rhabdoid tumor. Cancer Genet Cytogenet. 2008 Feb;181(1):67-8. PMID: #18262058#

- Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet. 2007 Apr;80(4):805-10. PMID: #17357086#

- hSNF5/INI1-deficient tumours and rhabdoid tumours are convergent but not fully overlapping entities. Bourdeaut F, Fréneaux P, Thuille B, Lellouch-Tubiana A, Nicolas A, Couturier J, Pierron G, Sainte-Rose C, Bergeron C, Bouvier R, Rialland X, Laurence V, Michon J, Sastre-Garau X, Delattre O. J Pathol. 2007 Feb;211(3):323-30. PMID: #17152049#

- Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex. Klochendler-Yeivin A, Picarsky E, Yaniv M. Mol Cell Biol. 2006 Apr;26(7):2661-74. PMID: #16537910# [Free]

- Rousseau-Merck MF, Fiette L, Klochendler-Yeivin A, Delattre O, Aurias A. Chromosome mechanisms and INI1 inactivation in human and mouse rhabdoid tumors. Cancer Genet Cytogenet. 2005 Mar;157(2):127-33. PMID: #15721633#

- Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Isakoff MS, Sansam CG, Tamayo P, Subramanian A, Evans JA, Fillmore CM, Wang X, Biegel JA, Pomeroy SL, Mesirov JP, Roberts CW. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17745-50. PMID: #16301525# [Free]

- Roberts CW, Orkin SH. The SWI/SNF complex—chromatin and cancer. Nat Rev Cancer. 2004 Feb;4(2):133-42. PMID: #14964309#

- Judkins AR, Mauger J, Ht A, Rorke LB, Biegel JA. Immunohistochemical Analysis of hSNF5/INI1 in Pediatric CNS Neoplasms. Am J Surg Pathol. 2004 May;28(5):644-650. PMID: #15105654#

- Biegel JA, Kalpana G, Knudsen ES, Packer RJ, Roberts CW, Thiele CJ, Weissman B, Smith M. The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res. 2002 Jan 1;62(1):323-8. PMID: #11782395#

- Biegel JA, Tan L, Zhang F, et al. Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin Cancer Res. 2002;8:3461-3467.

- Biegel JA, Zhou JY, Rorke LB, et al. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999;59:74-79.

- Burger PC, Yu IT, Tihan T, et al. Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study. Am J Surg Pathol. 1998;22:1083-1092.

- Gessi M, Giangaspero F, Pietsch T. Atypical teratoid/rhabdoid tumors and choroid plexus tumors: when genetics surprise pathology. Brain Pathol. 2003;13:409-414.

- Hilden JM, Meerbaum S, Burger P, et al. Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol. 2004;22:2877-2884.

- Hoot AC, Russo P, Judkins AR, et al. Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors. Am J Surg Pathol. 2004;28:1485-1491.

- Judkins AR, Burger PC, Hamilton RL, et al. INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol. 2005;64:391-397.

- The tumor suppressor hSNF5/INI1 modulates cell growth and actin cytoskeleton organization. Medjkane S, Novikov E, Versteege I, Delattre O. Cancer Res. 2004 May 15;64(10):3406-13. PMID: #15150092# [Free]

- Judkins AR, Mauger J, Ht A, et al. Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. Am J Surg Pathol. 2004;28:644-650.

- INI1 expression induces cell cycle arrest and markers of senescence in malignant rhabdoid tumor cells. Reincke BS, Rosson GB, Oswald BW, Wright CF. J Cell Physiol. 2003 Mar;194(3):303-13. PMID: #12548550#

- A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle. Versteege I, Medjkane S, Rouillard D, Delattre O. Oncogene. 2002 Sep 19;21(42):6403-12. PMID: #12226744# [Free]

- Re-expression of hSNF5/INI1/BAF47 in pediatric tumor cells leads to G1 arrest associated with induction of p16ink4a and activation of RB. Betz BL, Strobeck MW, Reisman DN, Knudsen ES, Weissman BE. Oncogene. 2002 Aug 8;21(34):5193-203. PMID: #12149641# [Free]

- Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells. Ae K, Kobayashi N, Sakuma R, Ogata T, Kuroda H, Kawaguchi N, Shinomiya K, Kitamura Y. Oncogene. 2002 May 9;21(20):3112-20. PMID: #12082626# [Free]

- Kalpana GV, Marmon S, Wang W, et al. Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science. 1994;266:2002-2006.

- Kleihues P, Cavenee WK. World Health Organization Classification of Tumours Pathology & Genetics Tumours of the Nervous System. Lyon: IARC Press; 2000.

- Kraus JA, Oster C, Sorensen N, et al. Human medulloblastomas lack point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene. Neuropathol Appl Neurobiol. 2002;28:136-141.

- Packer RJ, Biegel JA, Blaney S, et al. Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop. J Pediatr Hematol Oncol. 2002;24:337-342.

- Perry A, Fuller CE, Judkins AR, et al. INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas. Mod Pathol. 2005;18:951-958.

- Rorke LB, Biegel JA. Atypical teratoid/rhabdoid tumor. In: Kleihues P, Cavenee WK, eds. World Health Organization Classification of Tumours. Pathology & Genetics Tumours of the Nervous System. Lyon: IARC Press; 2000:145-148.

- Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg. 1996;85:56-65.

- Rosty C, Peter M, Zucman J, et al. Cytogenetic and molecular analysis of a t(1;22)(p36;q11.2) in a rhabdoid tumor with a putative homozygous deletion of chromosome 22. Genes Chromosomes Cancer. 1998;21:82-89.

- Rousseau-Merck MF, Versteege I, Legrand I, et al. hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors. Cancer Res. 1999;59:3152-3156.

- Sevenet N, Lellouch-Tubiana A, Schofield D, et al. Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet. 1999;8:2359-2368.

- Stock C, Ambros IM, Lion T, et al. Detection of numerical and structural chromosome abnormalities in pediatric germ cell tumors by means of interphase cytogenetics. Genes Chromosomes Cancer. 1994;11:40-50.

- Tekautz TM, Fuller CE, Blaney S, et al. Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol. 2005;23:1491-1499.

- Versteege I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394:203-206.


  • INI1/SNF5 (SMARCB1) negative immunostaining
  • INI1/SNF5 (SMARCB1) negative immunostaining
  • INI1/SNF5 (SMARCB1) negative immunostaining
  • INI1/SNF5 (SMARCB1) negative immunostaining
  • INI1/SNF5 in desmoplastic medulloblastoma
  • INI1/SNF5 in desmoplastic medulloblastoma