title: PTEN/MMAC1 mutations and EGFR amplification in glioblastomas.
abstract: Loss of heterozygosity (LOH) from chromosome 10 is a hallmark of glioblastoma, the most malignant (grade IV) form of glioma. A candidate tumor suppressor gene, PTEN/MMAC1, that may be targeted for deletion in association with chromosome 10 LOH has recently been identified. Here we have investigated 63 glioblastomas for PTEN/MMAC1 alterations and identified DNA sequence changes that would affect the encoded protein in 17 (27%) tumors. Microsatellite analyses of normal-tumor DNA pairs were performed on 14 of these cases and revealed LOH at locations flanking and/or near PTEN/MMAC1 in all but 1 instance, suggesting that deletion of the remaining wild-type allele had occurred in the large majority of tumors with PTEN/MMAC1 mutations. Competitive PCR assays were developed to address the possible occurrence of PTEN/MMAC1 homozygous deletions in glioblastomas, and this analysis identified three samples having loss of both PTEN/MMAC1 alleles. EGFR amplification was determined to occur at similar frequencies among cases with or without PTEN/MMAC1 homozygous deletions or mutations, suggesting that a growth-promoting effect resulting from amplification-associated increases in epidermal growth factor receptor signaling is not necessarily dependent on the inactivation of PTEN/MMAC1.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: C D
authors.initials: CD
authors.lastname: James
authors.forename: L
authors.initials: L
authors.lastname: Frederick
authors.forename: B E
authors.initials: BE
authors.lastname: Alderete
authors.forename: R B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004247:DNA / Q000097:blood; D004273:DNA, Neoplasm / Q000737:chemistry; D066246:ErbB Receptors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D016368:Frameshift Mutation; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D004247:DNA; D066246:ErbB Receptors; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human