Mutations of the INI1 rhabdoid tumor suppressor gene in medulloblastomas and primitive neuroectodermal tumors of the central nervous system

Germ-line and somatic mutations of the hSNF5/INI1 gene have been reported i n atypical teratoid/rhabdoid tumors (AT/RTs) of the brain, consistent with its role as a tumor suppressor gene. In the present study, we determined th e frequency of deletions and mutations of INI1 in 52 children whose origina l diagnosis was medulloblastoma (MB) or primitive neuroectodermal tumor (PN ET) of the central nervous system. Mutations were detected in DNA isolated from four tumors, all from children less than 3 years of age at diagnosis. Two of the four were reviewed and reclassified as atypical teratoid tumor, whereas there was insufficient material to establish this diagnosis in the two remaining cases, The relatively low frequency of mutations, even in a l arge series of infants, suggests that loss of sequences from chromosome 22 and/or mutations of INI1 do not account for the poor prognosis of children with IMB or PNET who are less than 3 years of age at diagnosis. Nevertheles s, chromosome 22 deletion and INI1-mutation analysis of infants with MB/PNE T should be considered for all children who are less than 1 year of age. De tection of these mutations suggests that the child has an AT/RT, rather tha n a MB/PNET, a finding with important prognostic value.