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APC mutations in sporadic medulloblastomas.

Abstract
The cerebellar medulloblastoma (WHO Grade IV) is a highly malignant, invasive embryonal tumor with preferential manifestation in children. Several molecular alterations appear to be involved, including isochromosome 17q and the p53, PTCH, and beta-catenin gene mutations. In this study, 46 sporadic medulloblastomas were screened for the presence of mutations in genes of the Wnt signaling pathway (APC and beta-catenin). Single-strand conformational polymorphism (SSCP) analysis followed by direct DNA sequencing revealed 3 miscoding APC mutations in 2 (4.3%) medulloblastomas. One case contained a GCA-->GTA mutation at codon 1296 (Ala-->Val), and another case had double point mutations at codons 1472 (GTA-->ATA, Val-->Ile) and 1495 (AGT-->GGT, Ser-->Gly). Miscoding beta-catenin mutations were detected in 4 tumors (8.7%). Three of these were located at codon 33 (TCT -->TTT, Ser-->Phe) and another at codon 37 (TCT-->GCT, Ser-->Ala). Adenomatous polyposis coli (APC) gene and beta-catenin mutations were mutually exclusive and occurred in a total of 6 of 46 cases (13%). Although germline APC mutations are a well established cause of familial colon and brain tumors (Turcot syndrome), this study provides the first evidence that APC mutations are also operative in a subset of sporadic medulloblastomas.
AuthorsH Huang, B M Mahler-Araujo, A Sankila, L Chimelli, Y Yonekawa, P Kleihues, H Ohgaki
JournalThe American journal of pathology (Am J Pathol) Vol. 156 Issue 2 Pg. 433-7 (Feb 2000) ISSN: 0002-9440 [Print] UNITED STATES
PMID10666372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA, Neoplasm
  • Trans-Activators
  • beta Catenin
Topics
  • Adenomatous Polyposis Coli Protein
  • Adolescent
  • Adult
  • Amino Acid Substitution
  • Base Sequence (genetics)
  • Cerebellar Neoplasms (genetics)
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins (genetics)
  • DNA, Neoplasm (genetics)
  • Female
  • Gene Frequency
  • Humans
  • Infant
  • Male
  • Medulloblastoma (genetics)
  • Middle Aged
  • Mutation
  • Point Mutation
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Trans-Activators
  • beta Catenin

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