Prompt identification of the germline SMARCB1 alteration and the resultant rhabdoid tumor predisposition syndrome can help guide genetic counseling and surveillance in affected family members.
SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in the large majority of rhabdoid tumors, and germline heterozygous SMARCB1 mutations form the basis for rhabdoid predisposition syndrome.
In conclusion, this study demonstrates for the first time transmission of a germline INI1-mutation in a RTPS family via nonpenetrant males, long-term survival of two members of this family with an AT/RT, and involvement of INI1 in the pathogenesis of myoepithelioma.
This is supported by the occurence of choroid plexus carcinomas (CPC) in the setting of families with rhabdoid predisposition syndrome (RPS), (19) caused by germ line inactivation of the INI1 gene.
The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene.
In the last decade, sporadic publications have shown that a different SWI/SNF protein, brahma-related gene 1 (BRG1), encoded by the <i>SMARCA4</i> gene, is associated with a similar rhabdoid phenotype and possible germline mutation termed rhabdoid tumor predisposition syndrome type 2.
Approximately one-third of pediatric malignant rhabdoid tumors are linked to germline SWI/SNF alterations (SMARCB1/INI1, rarely SMARCA4) resulting in occasional familial clustering of these highly aggressive malignancies (so-called rhabdoid tumor predisposition syndrome, RTPS, types 1 and 2, respectively).
SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in the large majority of rhabdoid tumors, and germline heterozygous SMARCB1 mutations form the basis for rhabdoid predisposition syndrome.