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.
Authors	H Huang, B M Mahler-Araujo, A Sankila, L Chimelli, Y Yonekawa, P Kleihues, H Ohgaki
Journal	The American journal of pathology (Am J Pathol) Vol. 156 Issue 2 Pg. 433-7 (Feb 2000) ISSN: 0002-9440 [Print] United States
PMID	10666372 (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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