Amplicons on chromosome 12q13-21 in glioblastoma recurrences.
There is limited knowledge on the in vivo behavior of amplified regions in human tumors. First evidence indicates that amplicon structures are largely maintained in recurrent tumors. Here, we investigated the fate of amplified regions in several independent cases of recurrent glioblastoma and the possible association of 12q13-21 amplifications and survival. We analyzed 12q13-21 amplicon numbers and sizes in glioblastoma and their recurrences by array-CGH. The majority of the 12q13-21 amplicons found in the original tumor are lost in the subsequent recurrence. Likewise, the majority of the amplicons found in the first recurrence are lost in the second recurrence. The remaining amplicons of recurrences often expanded or were maintained in size. Because of re-emergences and de novo appearances of amplicons, however, the overall number of amplicons did not decrease in the recurrences. Understanding genetic changes including gene amplifications in the development of tumor recurrences will contribute to rational therapeutic strategies for an improved patient survival. We recognized a significant longer survival time in glioblastoma patients that lack amplifications of either CDK4, CYP27B1, XRCC6BP1 (KUB3), or MDM2.
Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. hgufis@uniklinik-saarland.de
Ulrike
U
Fischer
Petra
P
Leidinger
Andreas
A
Keller
Amos
A
Folarin
Ralf
R
Ketter
Norbert
N
Graf
Hans-Peter
HP
Lenhof
Eckart
E
Meese
D000328:Adult; D000368:Aged; D001706:Biopsy; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence; D017741:Survivors