title: Retrospective family study of childhood medulloblastoma.
abstract: Medulloblastoma is the most common malignant central nervous system tumor of childhood and can occur sporadically or in association with inherited cancer susceptibility syndromes such as the nevoid basal cell carcinoma syndrome (NBCCS). To determine whether an association existed between the risk of developing medulloblastoma and undiagnosed syndromes, we retrospectively reviewed clinical data on 33 patients with medulloblastoma from a single institution and compared them with their unaffected relatives (n = 46). Six patients had tumors showing desmoplastic histology. Two of the six met diagnostic criteria for NBCCS. One NBCCS patient had a missense mutation of patched-1 (PTCH1); the other had no identifiable PTCH1 mutation. Two patients with isolated desmoplastic medulloblastoma had an insertion and splice site mutation, respectively, in suppressor of fused (SUFU). All patients with nondesmoplastic medulloblastoma histology received molecular testing for SUFU. None of these patients had an identifiable mutation in PTCH1 or SUFU. We performed a clinical evaluation for Greig cephalopolysyndactyly syndrome (GCPS) in four medulloblastoma families, who exhibited macrocephaly as the only finding consistent with the diagnosis of GCPS. Molecular analysis of GLI3 in these four families was negative. There was a paucity of clinical findings among the majority of medulloblastoma patients in this study group to suggest a definable cancer genetic syndrome. We conclude that clinically recognizable syndromes are uncommon among patients with medulloblastoma, however, PTCH1 and SUFU mutations are present at a low but significant frequency.
authors.affiliation: Genetic Epidemiology Branch, DCEG, NCI, NIH, DHHS, Bethesda, Maryland, USA. davidng@mail.nih.gov
authors.forename: David
authors.initials: D
authors.lastname: Ng
authors.forename: Theodora
authors.initials: T
authors.lastname: Stavrou
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Bert
authors.initials: B
authors.lastname: Gold
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelley
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Dubovsky
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vezina
authors.forename: H S
authors.initials: HS
authors.lastname: Nicholson
authors.forename: Julianne
authors.initials: J
authors.lastname: Byrne
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
authors.forename: David
authors.initials: D
authors.lastname: Hogg
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics; D000074290:Zinc Finger Protein Gli3
chemical_list: D004268:DNA-Binding Proteins; C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C490764:SUFU protein, human; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3; D004247:DNA