Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme

Glioblastoma multiforme (GEM) can be divided into genetic subsets: approximately one-third of GEM, primarily in older adults, have EGFR amplification; another one-third, primarily in younger adults, have TP53 mutation, The majority of GEM 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 GEM 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%) GEM. Of the 28 GEM with EGFR amplification, 20 (71%) had CDKN2 deletion (p = 0.0078), The remaining 16 cases with CDKN2 loss were divided between GEM with TP53 mutations (6 cases) and GEM with neither EGFR amplification nor TP53 mutation (10 cases), Thus, CDKN2 deletions occur twice as commonly in GEM with EGFR amplification (71%) than in GEM with TP53 mutation (29%), CDKN2 deletions occurred in GEM from patients somewhat older than those patients with GEM lacking CDKN2 deletion (mean age 53 vs, 48 years), Specifically among GEM with EGFR amplification, those with CDKN2 deletions also occurred in patients slightly older than those few GEM without CDKN2 deletions (mean age 55 vs, 51 years), The presence of CDKN2 deletions in most GEM with EGFR amplification and in generally older patients may provide one explanation for the potentially more aggressive nature of such tumors.