rhabdoid tumor predisposition syndrome

Familial or individual associations of

 malignant rhabdoid tumor
 cerebral atypical teratoid/rhabdoid tumor
 spinal canal or cerebral primitive neuroectodermal tumor (cPNET)

Etiology

2 loci

 germline SMARCB1 mutations
 other locus unknown

Molecular pathology

 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.

Prognosis

 highly aggressive tumor
 80% mortality rate with frequent metastases, predominantly pulmonary
 better outcome for girls (> 50% survival) than for boys (10%) (one study)

Links

 AGCOH

References

 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)

 Jackson EM, Shaikh TH, Gururangan S, Jones MC, Malkin D, Nikkel SM, Zuppan CW, Wainwright LM, Zhang F, Biegel JA. High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumor. Hum Genet. 2007 Sep;122(2):117-27. PMID: 17541642

 Frühwald MC, Hasselblatt M, Wirth S, Köhler G, Schneppenheim R, Subero JI, Siebert R, Kordes U, Jürgens H, Vormoor J. Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome. Pediatr Blood Cancer. 2006 Sep;47(3):273-8. PMID: 16206192

 Lee HY, Yoon CS, Sevenet N, Rajalingam V, Delattre O, Walford NQ. Rhabdoid tumor of the kidney is a component of the rhabdoid predisposition syndrome. Pediatr Dev Pathol. 2002 Jul-Aug;5(4):395-9. PMID: 12016529

 Fruhwald MC, Hasselblatt M, Wirth S, Kohler G, Schneppenheim R, Subero JI, Siebert R, Kordes U, Jurgens H, Vormoor J. Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome. Pediatr Blood Cancer. 2005 Oct 3; PMID: 16206192

 Vries RG, Bezrookove V, Zuijderduijn LM, Kia SK, Houweling A, Oruetxebarria I, Raap AK, Verrijzer CP. Cancer-associated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint. Genes Dev. 2005 Mar 15;19(6):665-70. PMID: 15769941

 Frühwald MC, Hasselblatt M, Wirth S, Köhler G, Schneppenheim R, Subero JI, Siebert R, Kordes U, Jürgens H, Vormoor J. Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome. Pediatr Blood Cancer. 2006 Sep;47(3):273-8. PMID: 16206192

 Kusafuka T, Miao J, Yoneda A, Kuroda S, Fukuzawa M. Novel germ-line deletion of SNF5/INI1/SMARCB1 gene in neonate presenting with congenital malignant rhabdoid tumor of kidney and brain primitive neuroectodermal tumor. Genes Chromosomes Cancer. 2004 Jun;40(2):133-9. PMID: 15101046

 Fujisawa H, Takabatake Y, Fukusato T, Tachibana O, Tsuchiya Y, Yamashita J. Molecular analysis of the rhabdoid predisposition syndrome in a child: a novel germline hSNF5/INI1 mutation and absence of c-myc amplification. J Neurooncol. 2003 Jul;63(3):257-62. PMID: 12892231

 Izycka-Swieszewska E, Debiec-Rychter M, Wasag B, Wozniak A, Gasecki D, Plata-Nazar K, Bartkowiak J, Lasota J, Limon J. A unique occurrence of a cerebral atypical teratoid/rhabdoid tumor in an infant and a spinal canal primitive neuroectodermal tumor in her father. J Neurooncol. 2003 Feb;61(3):219-25. PMID: 12675315

 Biegel JA, Fogelgren B, Wainwright LM, Zhou JY, Bevan H, Rorke LB. Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer. 2000 May;28(1):31-7. PMID: 10738300

 Taylor MD, Gokgoz N, Andrulis IL, Mainprize TG, Drake JM, Rutka JT. Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene. Am J Hum Genet. 2000 Apr;66(4):1403-6. PMID: 10739763

 Sevenet N, Sheridan E, Amram D, Schneider P, Handgretinger R, Delattre O. Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet. 1999 Nov;65(5):1342-8. PMID: 10521299