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Pediatric Cancer, Volume 3 pp 25–34Cite as

Paediatric Teratoid/Rhabdoid Tumours: Germline Deletions of Chromosome 22q11.2

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Part of the book series: Pediatric Cancer ((PECA,volume 3))

Abstract

The highly malignant rhabdoid tumours (MRTs) in particular atypical teratoid/rhabdoid tumours (AT/RT) are generally considered to be a childhood tumour with the majority of patients presenting at younger than 5 years of age. In most cases these tumours arise from inactivation of the INI1/SMARCB1 gene due to 22q11.2 deletions. Germline alterations of INI1/SMARCB1 have been found in up to 35% of patients with rhabdoid tumours. Patients with germline alterations generally present at an earlier age and with more aggressive disease, commonly with multiple primary tumours.

The chromosomal region on 22q11 is highly susceptible to microdeletions and microduplications due to the presence of several low copy repeats (LCR) within a 9 Mb region. The proximal deletion at 22q11.2 is the most well known microdeletion syndrome in this region and gives rise to DiGeorge/Velocardiofacial syndrome (DGS/VCFs). However the lesser known distal 22q11.2 deletion syndrome, when it encompasses the INI1/SMARCB1 gene, confers a high risk of developing AT/RT or MRT. Patients diagnosed with distal 22q11.2 deletion syndrome who also have rhabdoid predisposition syndrome due to loss of INI1/SMARCB1 should undergo careful monitoring due to their increased risk of developing these type of tumours.

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References

  • Beddow RA, Smith M, Kidd A, Corbett R, Hunter AG (2011) Diagnosis of distal 22q11.2 deletion syndrome in a patient with teratoid/rhabdoid tumour. Eur J Med Genet 54:295–298

    Article  CAS  PubMed  Google Scholar 

  • Ben-Shachar S, Ou Z, Shaw CA, Belmont JW, Patel MS, Hummel M, Amato S, Tartaglia N, Berg J, Reid SV, Lalani SR, Chinault C, Cheung SW, Lupski JR, Patel A (2008) 22q11.2 Distal deletion: a recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome. Am J Hum Genet 82:214–221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Biegel JA (2006) Molecular genetics of atypical teratoid/rhabdoid tumour. Neurosurg Focus 20:E11

    Article  PubMed  Google Scholar 

  • Biegel JA, Rourke LB, Packer RJ, Emanuel BS (1990) Monosomy22 in rhabdoid or atypical tumours of the brain. J Neurosurg 73:710–714

    Article  CAS  PubMed  Google Scholar 

  • Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelegren B (1999) Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumours. Cancer Res 59:74–79

    CAS  PubMed  Google Scholar 

  • Caramel J, Quignon F, Delattre O (2008) RhoA-dependent regulation of cell migration by the tumour suppressot hSNFs/INI1. Cancer Res 68:6154–6161

    Article  CAS  PubMed  Google Scholar 

  • Douglass EC, Valentine M, Rowe ST, Parham DM, Williams JA, Sanders JM, Houghton PJ (1990) Malignant rhabdoid tumor: a highly malignant childhood tumor with minimal karyotypic changes. Genes Chromosomes Cancer 2:210–216

    Article  CAS  PubMed  Google Scholar 

  • Eaton KW, Tooke LS, Wainwright LM, Judkins AR, Biegel JA (2011) Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer 56:7–15

    Article  PubMed Central  PubMed  Google Scholar 

  • Edelmann L, Pandita RK, Spiteri E, Funke B, Goldberg R, Palanisamy N, Chaganti RS, Magenis E, Shprintzen RJ, Morrow BE (1999) A common molecular basis for rearrangement disorders on 22q11. Hum Mol Genet 8:1157–1167

    Article  CAS  PubMed  Google Scholar 

  • Guo X, Freyer L, Morrow B, Zheng D (2011) Characterization of the past and current duplication activities in the human 22q11.2 region. BMC Genomics 12:71–87

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hoot AC, Russo P, Judkins AR, Perlman EJ, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumours from other pediatric soft tissue tumors. Am J Surg Pathol 28:1485–1791

    Article  PubMed  Google Scholar 

  • Jackson EM, Shaikh TH, Gururangan S, Jones MC, Malkin D, Nikkel SM, Zuppan CW, Wainwright LM, Zhang F, Biegel JA (2007) High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumour. Hum Genet 122:117–127

    Article  CAS  PubMed  Google Scholar 

  • Janson K, Nedzi LA, David O, Schorin M, Walsh JW, Bhattacharjee M, Pridjian G, Tan L, Judkins AR, Biegel JA (2006) Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation. Pediatr Blood Cancer 47:279–284

    Article  PubMed  Google Scholar 

  • Lafay-Cousin L, Payne E, Strother D, Chernos J, Chan M, Bernier FP (2009) Goldenhar phenotype in a child with distal 22q11.2 deletion and intracranial atypical teratoid rhabdoid tumour. Am J Med Genet 149A:2855–2859

    Article  PubMed  Google Scholar 

  • Lynch HT, Shurin SB, Dahms BB, Izant RJ, Lynch J, Danes BS (1983) Paravertebral malignant rhabdoid tumor in infancy. Cancer 52:290–296

    Article  CAS  PubMed  Google Scholar 

  • McKenna ES, Sansam CG, Cho YJ, Geulich H, Evans JA, Thom CS, Moreau LA, Biegel JA, Pomeroy SL, Roberts CWM (2008) Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic instability. Mol Cell Biol 28:6223–6233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Medjkane S, Novikov E, Verteege I, Delattre O (2004) The tumor suppressor hSNF5/INI1 modulates cell growth and actin cytoskeleton organisation. Cancer Res 64:3406–3413

    Article  CAS  PubMed  Google Scholar 

  • Mikhail FM, Descartes M, Piotrwski A, Andersson R, Diaz de Ståhl T, Komorowski J, Bruder CE, Dumanski JP, Carroll AJ (2007) A previously unrecognised microdeletion syndrome on chromosome 22 band q11.2 encompassing the BCR gene. Am J Med Genet A 143:2178–2184

    Article  Google Scholar 

  • Perez E, Sullivan K (2002) Chromosome 22q11.2 Deletion syndrome (DiGeorge and velocardiofacial syndromes). Curr Opin Pediatr 14:678–683

    Article  PubMed  Google Scholar 

  • Proust F, Laquerriere A, Costantin B, Ruchoux MM, Vannier JP, Freger P (1999) Simultaneous presentation of atypical teratoid/rhabdoid tumor in siblings. J Neuro Oncol 43:63–70

    Article  CAS  Google Scholar 

  • Raunch A, Pfeiffer RA, Leipold G, Singer H, Tigges M, Hofbeck MA (1999) A novel 22q11.2 Microdeletion in DiGeorge syndrome. Am J Hum Genet 64:659–667

    Article  Google Scholar 

  • Raunch A, Zink S, Zweier C, Thiel CT, Koch A, Rauch R, Lascorz J, Hüffmeier U, Weyand M, Singer H, Hofbeck M (2005) Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2. J Med Genet 42:871–876

    Article  Google Scholar 

  • Ravan JB, Tepperberg JH, Papenhausen P, Lamb AN, Hedrick J, Eash D, Ledbetter DH, Martin CL (2006) Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J Med Genet 43:478–489

    Article  Google Scholar 

  • Rickert CH, Paulus W (2001) Epidemiology of central nervous system tumours in childhood and adolescence based on the new WHO classification. Childs Nerv Syst 17:503–511

    Article  CAS  PubMed  Google Scholar 

  • Roberts CWM, Biegel JA (2009) The role of SMARCB1/INI1 in development of rhabdoid tumor. Cancer Biol Ther 8(5):412–416

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rødningen OK, Prescott T, Eriksson AS, Røsby O (2008) 1.4Mb recurrent 22q11.2 distal deletion syndrome, two new cases expand the phenotype. Eur J Med Genet 51:646–650

    Article  PubMed  Google Scholar 

  • Rousseau-Merk MF, Verteege I, Legrand I, Couturier J, Mairal A, Delattre O, Aurias A (1999) hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombination in rhabdoid tumour. Cancer Res 59:3152–3156

    Google Scholar 

  • Scambler PJ (2000) The 22q11 deletion syndromes. Hum Mol Genet 9:2421–2426

    Article  CAS  PubMed  Google Scholar 

  • Sévenet N, Sheridan E, Amram D, Schneider P, Handgretinge R, Delattre O (1999) Constitutional mutations of the hSNF/INI1 gene predispose to a variety of cancers. Am J Hum Genet 65:1342–1348

    Article  PubMed Central  PubMed  Google Scholar 

  • Shaikh TH, Kurahashi H, Emanuel BS (2001) Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions, duplications, translocations and genomic instability: an update and literature review. Genet Med 3:6–13

    Article  CAS  PubMed  Google Scholar 

  • Shaikh TH, O’Connor RJ, Pierpont ME, McGrath J, Hacker AM, Nimmakayalu M, Geiger E, Emanuel BS, Saitta SC (2007) Low copy repeats mediate distal chromosome 22q11.2 deletions: sequence analysis predicts breakpoint mechanisms. Genome Res 17:482–491

    Article  CAS  PubMed  Google Scholar 

  • Toth G, Zraly CB, Thomson TL, Jones C, Lapetino S, Murakas J, Zhang J, Dingwall AK (2011) Congenital anomalies and rhabdoid tumor associated with 22q11 germline deletion and somatic inactivation of the SMARCB1 tumor suppressor. Genes Chromosomes Cancer 50:379–388

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Versteege I, Sevenet N, Lange J, Rousseau-Merck M-F, Ambros P, Handgretinger R, Aurias A, Delattre O (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394:203–206

    Article  CAS  PubMed  Google Scholar 

  • Vries RGJ, Bezrookove V, Zuijderduijn LMP, Kia SK, Houweling A, Oruetxebarria I, Raap AK, Verrijzer CP (2005) Cancer-associated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint. Genes Dev 19:665–670

    Article  CAS  PubMed  Google Scholar 

  • Wieser R, Fritz B, Ullmann R, Müller I, Galhuber M, Storlazzi CT, Ramaswamy A, Christiansen H, Shimizu N, Rehder H (2005) Novel rearrangement of chromosome band 22q11.2 causing microdeletion syndrome-like phenotype and rhabdoid tumour of the kidney. Hum Mutat 26:78–83

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I would like to thank my friends and colleagues at Central and Southern Regional Genetic Services for their proof reading skills and Kathryn Seally for her help with Fig. 3.1.

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Authors and Affiliations

  1. Central and Southern Genetic Services, Wellington Hospital, 7902, Wellington, New Zealand

    Rachel Beddow

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  1. Rachel Beddow
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Correspondence to Rachel Beddow .

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  1. Biology, Kean University, Union, New Jersey, USA

    M.A. Hayat

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Beddow, R. (2012). Paediatric Teratoid/Rhabdoid Tumours: Germline Deletions of Chromosome 22q11.2. In: Hayat, M. (eds) Pediatric Cancer, Volume 3. Pediatric Cancer, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4528-5_3

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