Abstract
Two metachronous glioblastomas with different cerebral locations in a 53-year-old long-term survival patient were analyzed by multiple genetic approaches. Using comparative genomic hybridization a different pattern of chromosomal aberrations was observed, with 19 imbalances in the first tumor and only 2 imbalances in the second. Sequence analysis revealed a distinct mutation profile in each tumor, with amino acid substitutions in the p53 and PTEN genes only in the first tumor, ie, p53 in codon 273 (CGT-->TGT, Arg-->Cys) and PTEN in codon 336 (TAC-->TTC, Tyr-->Phe). A splicing acceptor site PTEN mutation (IVS8-2A>G) was observed only in the second GBM. EGFR amplification, mutations of p16INK4a/CDKN2A or p14ARF were not observed. According to the results of p53 mutational analysis and EGFR amplification studies, the first tumor is classified as a type 1 GBM, whereas the alterations in the second one are different from those typically encountered in type 1 or type 2 tumors. In conclusion, our data strongly suggest that the metachronous tumors in this patient are exceptional in that they developed independently from each other. Whether the molecular features of the first glioblastoma are associated with the notably extended recurrence-free period of 5 years remains to be elucidated.
Publication types
-
Case Reports
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Brain Neoplasms / genetics*
-
Brain Neoplasms / pathology
-
Brain Neoplasms / therapy
-
Chromosome Mapping
-
Chromosomes, Human, Pair 10
-
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
-
DNA Mutational Analysis
-
DNA-Binding Proteins*
-
Genes, erbB-1
-
Glial Fibrillary Acidic Protein / metabolism
-
Glioblastoma / diagnosis
-
Glioblastoma / genetics*
-
Glioblastoma / pathology
-
Glioblastoma / therapy
-
Humans
-
Immunohistochemistry
-
Keratins / metabolism
-
Ki-67 Antigen / metabolism
-
Loss of Heterozygosity
-
Magnetic Resonance Imaging / methods
-
Male
-
Middle Aged
-
MutS Homolog 2 Protein
-
Neoplasms, Second Primary / diagnosis
-
Neoplasms, Second Primary / genetics*
-
Neoplasms, Second Primary / pathology
-
Neoplasms, Second Primary / therapy
-
Nerve Tissue Proteins / metabolism
-
PTEN Phosphohydrolase
-
Phosphoric Monoester Hydrolases / genetics*
-
Phosphoric Monoester Hydrolases / metabolism
-
Polymerase Chain Reaction / methods
-
Proto-Oncogene Proteins / metabolism
-
S100 Proteins / metabolism
-
Sequence Analysis, DNA / methods
-
Staining and Labeling
-
Tumor Suppressor Protein p53 / genetics*
-
Tumor Suppressor Protein p53 / metabolism
-
Tumor Suppressor Proteins / genetics*
-
Tumor Suppressor Proteins / metabolism
-
Vimentin / metabolism
Substances
-
Cyclin-Dependent Kinase Inhibitor p16
-
DNA-Binding Proteins
-
Glial Fibrillary Acidic Protein
-
Ki-67 Antigen
-
Nerve Tissue Proteins
-
Proto-Oncogene Proteins
-
S100 Proteins
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
Vimentin
-
heparin-binding neurite-promoting factor, p18
-
Keratins
-
Phosphoric Monoester Hydrolases
-
PTEN Phosphohydrolase
-
PTEN protein, human
-
MSH2 protein, human
-
MutS Homolog 2 Protein