A different view on DNA amplifications indicates frequent, highly complex, and stable amplicons on 12q13-21 in glioma. Fischer, U., Keller, A., Leidinger, P., Deutscher, S., Heisel, S., Urbschat, S., Lenhof, H., & Meese, E. Molecular cancer research : MCR, 6:576–584, April, 2008.
doi  abstract   bibtex   
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.
@Article{Fischer2008,
  author          = {Fischer, Ulrike and Keller, Andreas and Leidinger, Petra and Deutscher, Stephanie and Heisel, Sabrina and Urbschat, Steffi and Lenhof, Hans-Peter and Meese, Eckart},
  title           = {A different view on DNA amplifications indicates frequent, highly complex, and stable amplicons on 12q13-21 in glioma.},
  journal         = {Molecular cancer research : MCR},
  year            = {2008},
  volume          = {6},
  pages           = {576--584},
  month           = apr,
  issn            = {1541-7786},
  abstract        = {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.},
  chemicals       = {Carbocyanines, DNA, Neoplasm, cyanine dye 3, cyanine dye 5},
  citation-subset = {IM},
  completed       = {2008-07-07},
  country         = {United States},
  doi             = {10.1158/1541-7786.MCR-07-0283},
  issn-linking    = {1541-7786},
  issue           = {4},
  keywords        = {Adult; Aged; Blotting, Southern; Carbocyanines; Child; Child, Preschool; Chromosomes, Artificial, Bacterial; Chromosomes, Human, Pair 12, genetics; Computational Biology; Cosmids; DNA, Neoplasm, genetics; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Glioma, genetics; Humans; In Situ Hybridization, Fluorescence; Male; Middle Aged; Oligonucleotide Array Sequence Analysis},
  nlm-id          = {101150042},
  owner           = {NLM},
  pii             = {6/4/576},
  pmid            = {18403636},
  pubmodel        = {Print},
  pubstatus       = {ppublish},
  revised         = {2008-04-11},
}
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