tumors. In particular, the chromosomal 22 deletion is very common in AT/RTs. The chromosome 22 area contains the hSNF5/INI1 gene that appears to function as a classic tumor suppressor gene. Most rhabdoid tumors have INI1 deletions whether they occur in the CNS, kidney, or elsewhere. This mutation is viewed as the "first hit" which predisposes children to malignancies. INI1/hSNF5, a component of the chromatin remodeling SWI/SNF complex, is a critical tumor suppressor biallelically inactivated in rhabdoid tumors. Identification of INI1 as a tumor suppressor has facilitated accurate diagnosis of rhabdoid tumors. The rate of transcription for SWI/SNF and HDAC complexes seem to be regulated by the INI1 gene. The SWI/SNF complex plays a role in chromatin remodeling. AT/RT is the first pediatric brain tumor for which a candidate tumor suppressor gene has been identified. A mutation or deletion in the INI1/hSNF5 gene occurs in the majority of AT/RT tumors. Up to 90% of AT/RT cases involve chromosome 22 deletion. This is mainly point mutations in the hSNF5/INI1 gene (i.e., one can diagnosis AT/RT without a chromosome 22 deletion elsewhere). The hSNF5/INI1 gene regulates 15 or so proteins in the chromatin structure. In addition, the OPN gene has a higher expression in AT/RT tumors. All of the AT/RT cancers are believed to be not associated with the hSNF5/INI1 gene, as 14 additional proteins in the chromatin structure are controlled by other genes. There are also some emerging mouse models of the AT/RT cancer as well as experimental cell lines derived from tumors. Despite these advances, the function of the gene is not yet understood. There is not enough known about the function of INI1, either as an independent modulator of gene expression or through its association with the SWI/SNF complex, to be able to use specific targeted biological agents for treatment. Prospective clinical and biologic trials are greatly needed to understand the efficacy of therapeutic interventions, as well as the role of the gene. Risk for siblings and other members of the family Atypical teratoid/rhabdoid tumors are very rare, and absolute risk to siblings is not reported in the literature. However, some reports exist of AT/RTs presenting in two members of the same family, or one family member with an AT/RT and another with a renal rhabdoid tumor or other CNS tumor. These are suspected to arise from germline genetic mutations in a parent shared by affected siblings. A three-generation family