A different view on DNA amplifications indicates frequent, highly complex, and stable amplicons on 12q13-21 in glioma.
To further understand the biological significance of amplifications for glioma development and recurrencies, we characterized amplicon frequency and size in low-grade glioma and amplicon stability in vivo in recurring glioblastoma. We developed a 12q13-21 amplicon-specific genomic microarray and a bioinformatics amplification prediction tool to analyze amplicon frequency, size, and maintenance in 40 glioma samples including 16 glioblastoma, 10 anaplastic astrocytoma, 7 astrocytoma WHO grade 2, and 7 pilocytic astrocytoma. Whereas previous studies reported two amplified subregions, we found a more complex situation with many amplified subregions. Analyzing 40 glioma, we found that all analyzed glioblastoma and the majority of pilocytic astrocytoma, grade 2 astrocytoma, and anaplastic astrocytoma showed at least one amplified subregion, indicating a much higher amplification frequency than previously suggested. Amplifications in low-grade glioma were smaller in size and displayed clearly different distribution patterns than amplifications in glioblastoma. One glioblastoma and its recurrencies revealed an amplified subregion of 5 Mb that was stable for 6 years. Expression analysis of the amplified region revealed 10 overexpressed genes (i.e., KUB3, CTDSP2, CDK4, OS-9, DCTN2, RAB3IP, FRS2, GAS41, MDM2, and RAP1B) that were consistently overexpressed in all cases that carried this amplification. Our data indicate that amplifications on 12q13-21 (a) are more frequent than previously thought and present in low-grade tumors and (b) are maintained as extended regions over long periods of time.
Fischer
Ulrike
U
Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. hgufis@uniklinik-saarland.de
Keller
Andreas
A
Leidinger
Petra
P
Deutscher
Stephanie
S
Heisel
Sabrina
S
Urbschat
Steffi
S
Lenhof
Hans-Peter
HP
Meese
Eckart
E
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002232:Carbocyanines; D002648:Child; D002675:Child, Preschool; D022202:Chromosomes, Artificial, Bacterial; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D019295:Computational Biology; D003360:Cosmids; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D005910:Glioma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
D002232:Carbocyanines; D004273:DNA, Neoplasm; C089187:cyanine dye 3; C085321:cyanine dye 5