title: Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene.
abstract: High-frequent microsatellite instability (MSI-H) was detected in two of the 80 gliomas examined, whlie the other 78 gliomas showed microsatellite stable (MSS) phenotype. Both of the two MSI-H tumors were glioblastomas which developed in teenage patients. One of the patient was diagnosed as having Turcot's syndrome and had a germline mutation in the hMLH1 gene. Loss of expression due to promoter methylation was selectively observed in the wild type allele of the hMLH1 gene in the tumor of this patient. The other patient had neither a family history nor a past personal history of malignancy. Although no mutation in the mismatch repair genes was detected in the tumor of this patient, the level of expression of the hMLH1 gene was markedly decreased and the promoter sequence of the gene was highly methylated. In the tumor of this patient, the PTEN1 gene, one of the genes carrying microsatellite sequences in their coding regions, was altered by a slippage mutation within five adenine repeat sequences. These findings indicate that the genetic or epigenentic inactivation of the hMLH1 gene is involved in a subset of early-onset gliomas and the PTEN1 gene could be a downstream target for mutation as observed in glioblastoma without MSI.
authors.affiliation: Oncogene Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kanamori
authors.forename: H
authors.initials: H
authors.lastname: Kon
authors.forename: T
authors.initials: T
authors.lastname: Nobukuni
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Sugano
authors.forename: S
authors.initials: S
authors.lastname: Mashiyama
authors.forename: T
authors.initials: T
authors.lastname: Kumabe
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: M
authors.initials: M
authors.lastname: Meuth
authors.forename: T
authors.initials: T
authors.lastname: Sekiya
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017668:Age of Onset; D002352:Carrier Proteins; D019175:DNA Methylation; D020868:Gene Silencing; D018095:Germ-Line Mutation; D005910:Glioma / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009423:Nervous System Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1