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 in atypical teratoid/rhabdoid tumors (AT/RTs) of the brain, consistent with its role as a tumor suppressor gene. In the present study, we determined the frequency of deletions and mutations of INI1 in 52 children whose original diagnosis was medulloblastoma (MB) or primitive neuroectodermal tumor (PNET) 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 large 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 MB or PNET who are less than 3 years of age at diagnosis. Nevertheless, chromosome 22 deletion and INI1-mutation analysis of infants with MB/PNET should be considered for all children who are less than 1 year of age. Detection of these mutations suggests that the child has an AT/RT, rather than a MB/PNET, a finding with important prognostic value.
Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA. biegel@mail.med.upenn.edu
J A
JA
Biegel
B
B
Fogelgren
J Y
JY
Zhou
C D
CD
James
A J
AJ
Janss
J C
JC
Allen
D
D
Zagzag
C
C
Raffel
L B
LB
Rorke
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D016368:Frameshift Mutation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D019656:Loss of Heterozygosity; D008527:Medulloblastoma / Q000235:genetics* / Q000601:surgery; D009006:Monosomy; D009154:Mutation; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000601:surgery; D000071796:SMARCB1 Protein; D017384:Sequence Deletion; D014157:Transcription Factors
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors