Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme.
Glioblastoma multiforme (GBM) can be divided into genetic subsets: approximately one-third of GBM, primarily in older adults, have EGFR amplification; another one-third, primarily in younger adults, have TP53 mutation. The majority of GBM also have homozygous deletions of the CDKN2 (p16/MTS1) gene, resulting in cell cycle deregulation and elevated proliferation indices. We evaluated the relationship between CDKN2 deletions and the GBM subsets as defined by EGFR amplification or TP53 mutation in 70 GBM. Twenty-eight cases (40%) had EGFR amplification, 21 (30%) had TP53 mutation, and 21 (30%) had neither change. CDKN2 deletions were present in 36 (51%) GBM. Of the 28 GBM with EGFR amplification, 20 (71%) had CDKN2 deletion (p = 0.0078). The remaining 16 cases with CDKN2 loss were divided between GBM with TP53 mutations (6 cases) and GBM with neither EGFR amplification nor TP53 mutation (10 cases). Thus, CDKN2 deletions occur twice as commonly in GBM with EGFR amplification (71%) than in GBM with TP53 mutation (29%). CDKN2 deletions occurred in GBM from patients somewhat older than those patients with GBM lacking CDKN2 deletion (mean age 53 vs. 48 years). Specifically among GBM with EGFR amplification, those with CDKN2 deletions also occurred in patients slightly older than those few GBM without CDKN2 deletions (mean age 55 vs. 51 years). The presence of CDKN2 deletions in most GBM with EGFR amplification and in generally older patients may provide one explanation for the potentially more aggressive nature of such tumors.
Hayashi
Y
Y
Institut für Neuropathologie, Universitätskliniken Bonn, Germany.
Ueki
K
K
Waha
A
A
Wiestler
O D
OD
Louis
D N
DN
von Deimling
A
A
D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000235:genetics*; D005784:Gene Amplification; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008875:Middle Aged
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors