RHABDOID TUMOURS PREDISPOSITION SYNDROME 1
Rhabdoid Tumours are malignant, aggressive neoplasms that usually arise in infancy and early childhood. When these Tumours occur in the brain and spinal cord, they are referred to as atypical teratoid/rhabdoid Tumours (AT/RT), and when they arise in the kidney and/or soft tissues, they are termed malignant rhabdoid Tumours (MRT) or extra-cranial rhabdoid Tumours. Homozygous deletions on chromosome 22q, involving the SNF5/INI1 gene (sucrose nonfermenting 5/integrase interactor 1), now known as SMARCB1/BAF47, were reported in cell lines derived from malignant rhabdoid Tumours (Versteege et al. 1998). The SMARCB1 protein and other family members such as BRG1/SMARCA4 and ARID1A/SMARCF1 are involved in chromatin remodeling (Wilson and Roberts 2011). Subsequently, germline mutations were identified in children with ATRT and MRT (Sevenet et al. 1999; Biegel et al. 1999; Taylor et al. 2000). One-third of children with ATRT/MRT carry germline SMARCB1 mutations, and in about a quarter of cases, transmission from parent to child is reported, implying a less aggressive phenotype in the parent (Eaton et al. 2011). Compared to sporadic cases (untested or negative for SMARCB1 mutations), familial cases, mostly with germline SMARCB1 mutations, had earlier onset of more aggressive, widespread disease that was more likely to be fatal (Bruggers et al. 2011). An antibody to BAF47 (encoded by SMARCB1) is available and can be used as a screening step prior to germline mutation analysis since SMARCB1 appears to be a classical ‘two-hit’ Tumours suppressor (Roberts and Biegel 2009). Germline SMARCB1 mutations can also result in familial schwannomatosis, and occasionally, both ATRT and schwannomatosis have been reported in the same family (Carter et al. 2012).