PMID- 20570930 OWN - NLM STAT- MEDLINE DCOM- 20100901 LR - 20220129 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 16 IP - 13 DP - 2010 Jul 1 TI - A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. PG - 3368-77 LID - 10.1158/1078-0432.CCR-10-0438 [doi] AB - PURPOSE: As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors. EXPERIMENTAL DESIGN: We carried out copy number profiling by array comparative genomic hybridization using a 32K bacterial artificial chromosome platform on 63 formalin-fixed paraffin-embedded cases of high-grade glioma arising in children and young people (<23 years). RESULTS: The genomic profiles of these tumors could be subclassified into four categories: those with stable genomes, which were associated with a better prognosis; those with aneuploid and those with highly rearranged genomes; and those with an amplifier genotype, which had a significantly worse clinical outcome. Independent of this was a clear segregation of cases with 1q gain (more common in children) from those with concurrent 7 gain/10q loss (a defining feature of adults). Detailed mapping of all the amplification and deletion events revealed numerous low-frequency amplifications, including IGF1R, PDGFRB, PIK3CA, CDK6, CCND1, and CCNE1, and novel homozygous deletions encompassing unknown genes, including those at 5q35, 10q25, and 22q13. Despite this, aberrations targeting the "core signaling pathways" in adult glioblastomas are significantly underrepresented in the pediatric setting. CONCLUSIONS: These data highlight that although there are overlaps in the genomic events driving gliomagenesis of all ages, the pediatric disease harbors a distinct spectrum of copy number aberrations compared with adults. FAU - Bax, Dorine A AU - Bax DA AD - Section of Paediatric Oncology, The Institute of Cancer Research, Royal Marsden Hospital, Sutton, United Kingdom. FAU - Mackay, Alan AU - Mackay A FAU - Little, Suzanne E AU - Little SE FAU - Carvalho, Diana AU - Carvalho D FAU - Viana-Pereira, Marta AU - Viana-Pereira M FAU - Tamber, Narinder AU - Tamber N FAU - Grigoriadis, Anita E AU - Grigoriadis AE FAU - Ashworth, Alan AU - Ashworth A FAU - Reis, Rui M AU - Reis RM FAU - Ellison, David W AU - Ellison DW FAU - Al-Sarraj, Safa AU - Al-Sarraj S FAU - Hargrave, Darren AU - Hargrave D FAU - Jones, Chris AU - Jones C LA - eng GR - A6718/CRUK_/Cancer Research UK/United Kingdom GR - BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100622 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 SB - IM MH - Adolescent MH - Adult MH - Brain Neoplasms/*genetics MH - Child MH - Child, Preschool MH - Comparative Genomic Hybridization MH - *DNA Copy Number Variations MH - Gene Amplification MH - Gene Deletion MH - Glioblastoma/genetics MH - Glioma/*genetics MH - Humans PMC - PMC2896553 MID - UKMS30567 OID - NLM: UKMS30567 EDAT- 2010/06/24 06:00 MHDA- 2010/09/02 06:00 PMCR- 2011/01/01 CRDT- 2010/06/24 06:00 PHST- 2010/06/24 06:00 [entrez] PHST- 2010/06/24 06:00 [pubmed] PHST- 2010/09/02 06:00 [medline] PHST- 2011/01/01 00:00 [pmc-release] AID - 1078-0432.CCR-10-0438 [pii] AID - 10.1158/1078-0432.CCR-10-0438 [doi] PST - ppublish SO - Clin Cancer Res. 2010 Jul 1;16(13):3368-77. doi: 10.1158/1078-0432.CCR-10-0438. Epub 2010 Jun 22.