A survey of glioblastoma genomic amplifications and deletions.
Glioblastoma Multiforme (GBM) is a malignant brain cancer that develops after accumulating genomic DNA damage that often includes gene amplifications and/or deletions. These copy number changes can be a critical step in brain tumor development. To evaluate glioblastoma genomic copy number changes, we determined the genome-wide copy number alterations in 31 GBMs. Illumina Bead Arrays were used to assay 22 GBMs and Digital Karyotyping was used on 8 GBM cell lines and one primary sample. The common amplifications we observed for all 31 samples was GLI/CDK4 (22.6%), MDM2 (12.9%) and PIK3C2B/MDM4 (12.9%). In the 22 GBM tumors, EGFR was amplified in 22.7% of surgical biopsies. The most common homozygously deleted region contained CDKN2A/CDKN2B (p15 and p16) occurring in 29% of cases. This data was compiled and compared to published array CGH studies of 456 cases of GBMs. Pooling our Illumina data with published studies yielded these average amplification rates: EGFR-35.7%, GLI/CDK4-13.4%, MDM2-9.2%, PIK3C2B/MDM4-7.7%, and PDGFRA-7.7%. The CDKN2A/CDKN2B locus was deleted in 46.4% of the combined cases. This study provides a larger assessment of amplifications and deletions in glioblastoma patient populations and shows that several different copy number technologies can produce similar results. The main pathways known to be involved in GBM tumor formation such as p53 control, growth signaling, and cell cycle control are all represented by amplifications or deletions of critical pathway genes. This information is potentially important for formulating targeted therapy in glioblastoma and for planning genomic studies.
Rao
Shailaja K
SK
Department of Neurosurgery, Johns Hopkins University, CRB II Rm. 257, 1550 Orleans Street, Baltimore, MD 21231, USA.
Edwards
Jennifer
J
Joshi
Avadhut D
AD
Siu
I-Mei
IM
Riggins
Gregory J
GJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000502:physiology*; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017384:Sequence Deletion / Q000235:genetics