Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor

Franck Bourdeaut, Delphine Lequin, Laurence Brugières, Stéphanie Reynaud, Christelle Dufour, François Doz, Nicolas André, Jean Louis Stephan, Yves Pérel, Odile Oberlin, Daniel Orbach, Christophe Bergeron, Xavier Rialland, Paul Fréneaux, Dominique Ranchere, Dominique Figarella-Branger, Georges Audry, Stéphanie Puget, D. Gareth Evans, Joan Carles Ferreres PinasValeria Capra, Véronique Mosseri, Isabelle Coupier, Marion Gauthier-Villars, Gaelle Pierron, Olivier Delattre

Research output: Contribution to journalArticlepeer-review


Purpose: Germline hSNF5/INI1 mutations are responsible for hereditary cases of rhabdoid tumors (RT) that constitute the rhabdoid predisposition syndrome (RPS). Our study provides the first precise overview of the prevalence of RPS within a large cohort of RT. Experimental Design: hSNF5/INI1 coding exons were investigated by sequencing and by multiplex ligation-dependent probe amplification. Results: Seventy-four constitutional DNAs from 115 apparently sporadic RT were analyzed from 1999 to 2009. Germline mutations were found in 26 patients (35%). Data from 9 individuals from 5 RPS families (siblings) were also studied. The median age at diagnosis was much lower (6 months) in patients with germline mutation (P <0.01) than in patients without (18 months). Nevertheless, 7 of 35 patients with germline mutation (20%) developed the disease after 2 years of age. The mutation could be detected in only 1 parent whereas germline blood DNA was wild type in the 20 other parent pairs, therefore indicating the very high proportion of germ-cell mosaicism or of de novo mutations in RPS. The former hypothesis could be clearly documented in 1 case in which prenatal diagnosis was positive in a new pregnancy. Finally, the 2 years' overall survival was 7% in mutated and 29% in wild-type patients, mainly due to the worse outcome of RT in younger patients. Conclusions: Our results show 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. Genetic counseling is recommended given the low but actual risk of familial recurrence.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalClinical Cancer Research
Issue number1
Publication statusPublished - Jan 1 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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