title: Deletion analysis of the adenomatous polyposis coli and PTCH gene loci in patients with sporadic and nevoid basal cell carcinoma syndrome-associated medulloblastoma.
abstract: BACKGROUND
  Medulloblastomas can occur sporadically or may be associated with hereditary tumor syndromes including familial adenomatous polyposis (FAP) and nevoid basal cell carcinoma syndrome (NBCCS).
  
  
  METHODS
  The authors performed a retrospective analysis for allelic deletion of the adenomatous polyposis coli (APC) and PTCH gene loci using paraffin embedded medulloblastoma specimens from patients who were admitted to Children's National Medical Center in Washington, DC, between 1982 and 1997. Thirty-five cases from which tumor and normal tissue could be procured were analyzed. Two of the analyzed cases had a positive family and personal history for NBCCS; in both cases the histology of the medulloblastoma revealed a desmoplastic phenotype. Thirty-three cases were not known to be associated with hereditary disease; 2 of those cases revealed desmoplastic and 31 cases revealed nondesmoplastic "classic" medulloblastoma histology.
  
  
  RESULTS
  Although medulloblastoma tumorigenesis has been associated strongly with FAP associated with APC germline mutation, none of the 22 informative sporadic cases revealed loss of heterozygosity of the APC gene locus. PTCH gene deletion was detected in the tumors of both patients with NBCCS. In contrast, only 1 of 33 sporadic medulloblastomas revealed PTCH gene deletion. The sporadic case with PTCH gene deletion did not demonstrate the desmoplastic phenotype.
  
  
  CONCLUSIONS
  In conjunction with previous studies, the data from the current study confirm that allelic deletion occurs in NBCCS-associated medulloblastomas, consistent with the role of PTCH as a tumor suppressor gene. However, in sporadic medulloblastomas, allelic deletion of PTCH is an infrequent event. Morphologic examination in conjunction with genetic analysis of PTCH gene deletion in medulloblastoma tissue may prove to be a quick and efficient test with which to screen for NBCCS in patients with medulloblastomas. Although medulloblastoma is a component of Turcot syndrome with demonstrated APC mutations, APC gene deletions appear to be absent or very uncommon in patients with sporadic and NBCCS-associated medulloblastomas.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: A O
authors.initials: AO
authors.lastname: Vortmeyer
authors.forename: T
authors.initials: T
authors.lastname: Stavrou
authors.forename: D
authors.initials: D
authors.lastname: Selby
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: R J
authors.initials: RJ
authors.lastname: Weil
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: Y W
authors.initials: YW
authors.lastname: Moon
authors.forename: R
authors.initials: R
authors.lastname: Chandra
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Z
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D001478:Basal Cell Nevus Syndrome / Q000150:complications / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies