Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome
Article first published online: 3 OCT 2005
Copyright © 2005 Wiley-Liss, Inc.
Pediatric Blood & Cancer
Volume 47, Issue 3, pages 273–278, September 2006
How to Cite
Frühwald, M. C., Hasselblatt, M., Wirth, S., Köhler, G., Schneppenheim, R., Subero, J. I. M., Siebert, R., Kordes, U., Jürgens, H. and Vormoor, J. (2006), Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome. Pediatr. Blood Cancer, 47: 273–278. doi: 10.1002/pbc.20526
- Issue published online: 7 JUL 2006
- Article first published online: 3 OCT 2005
- Manuscript Accepted: 3 JUN 2005
- Manuscript Received: 11 MAY 2005
- the Sonja Wasowicz-Stiftung
- the Karl-Bröcker Stiftung
- the Fördergemeinschaft Kinderkrebszentrum Hamburg e.V.
- atypical teratoid/rhabdoid tumor;
- embryonal tumor;
- rhabdoid tumors;
- rhabdoid tumor predisposition syndrome;
Rhabdoid tumors represent an independent entity among embryonal neoplasms. These tumors affect the kidney (RTK, rhabdoid tumor of kidney) and central nervous system (AT/RT, atypical teratoid, rhabdoid tumor), but may also be found in peripheral soft tissue. Unifying features include immunohistochemical characteristics and inactivation of the putative tumor suppressor gene SMARCB1 (hSNF5/INI1) in chromosome 22q11.2. Several familial cases have been published and summarized under the term rhabdoid tumor predisposition syndrome. In all of the published familial cases, inactivation of SMARCB1 was detected in tumor tissues.
Procedure and Results
We report on a family with three children, two of which were affected by rhabdoid tumors, one RTK, the other an AT/RT. While both children demonstrated typical morphological and clinical features neither the RTK nor the AT/RT showed evidence for inactivation of SMARCB1 in molecular studies including CGH and array CGH, FISH, gene dosage analysis by dHPLC, and DNA-sequencing. Immunohistochemistry for SMARCB1 showed normal expression within the nuclei of tumor cells. Furthermore, both children inherited different paternal and maternal SMARCB1 alleles evidenced by haplotype analysis. Conventional cytogenetic, FISH, and mutation analyses lacked evidence for SMARCB1 aberrations or gross chromosomal changes in the parents.
We thus demonstrate a family with rhabdoid tumor predisposition syndrome without linkage to SMARCB1. This finding indicates that other loci than SMARCB1 below the resolution of array CGH are involved in the origin of these tumors. Our data impact on the clinical counseling of affected families and warrant further studies in the molecular biology of these enigmatic tumors. Pediatr Blood Cancer 2006;47:273–278. © 2005 Wiley-Liss, Inc.