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.
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.
Authors: Marie de Tayrac; Amandine Etcheverry; Marc Aubry; Stephan Saïkali; Abderrahmane Hamlat; Veronique Quillien; André Le Treut; Marie-Dominique Galibert; Jean Mosser Journal: Genes Chromosomes Cancer Date: 2009-01 Impact factor: 5.006
Authors: Barbara S Paugh; Alberto Broniscer; Chunxu Qu; Claudia P Miller; Junyuan Zhang; Ruth G Tatevossian; James M Olson; J Russell Geyer; Susan N Chi; Nasjla Saba da Silva; Arzu Onar-Thomas; Justin N Baker; Amar Gajjar; David W Ellison; Suzanne J Baker Journal: J Clin Oncol Date: 2011-09-19 Impact factor: 44.544
Authors: Jeremy Schwartzentruber; Andrey Korshunov; Xiao-Yang Liu; David T W Jones; Elke Pfaff; Karine Jacob; Dominik Sturm; Adam M Fontebasso; Dong-Anh Khuong Quang; Martje Tönjes; Volker Hovestadt; Steffen Albrecht; Marcel Kool; Andre Nantel; Carolin Konermann; Anders Lindroth; Natalie Jäger; Tobias Rausch; Marina Ryzhova; Jan O Korbel; Thomas Hielscher; Peter Hauser; Miklos Garami; Almos Klekner; Laszlo Bognar; Martin Ebinger; Martin U Schuhmann; Wolfram Scheurlen; Arnulf Pekrun; Michael C Frühwald; Wolfgang Roggendorf; Christoph Kramm; Matthias Dürken; Jeffrey Atkinson; Pierre Lepage; Alexandre Montpetit; Magdalena Zakrzewska; Krzystof Zakrzewski; Pawel P Liberski; Zhifeng Dong; Peter Siegel; Andreas E Kulozik; Marc Zapatka; Abhijit Guha; David Malkin; Jörg Felsberg; Guido Reifenberger; Andreas von Deimling; Koichi Ichimura; V Peter Collins; Hendrik Witt; Till Milde; Olaf Witt; Cindy Zhang; Pedro Castelo-Branco; Peter Lichter; Damien Faury; Uri Tabori; Christoph Plass; Jacek Majewski; Stefan M Pfister; Nada Jabado Journal: Nature Date: 2012-01-29 Impact factor: 49.962
Authors: Aleksandra Bielen; Lara Perryman; Gary M Box; Melanie Valenti; Alexis de Haven Brandon; Vanessa Martins; Alexa Jury; Sergey Popov; Sharon Gowan; Sebastien Jeay; Florence I Raynaud; Francesco Hofmann; Darren Hargrave; Suzanne A Eccles; Chris Jones Journal: Mol Cancer Ther Date: 2011-06-09 Impact factor: 6.261
Authors: Darren Hargrave; Birgit Geoerger; Didier Frappaz; Torsten Pietsch; Lyle Gesner; Laura Cisar; Aurora Breazna; Andrew Dorman; Ofelia Cruz-Martinez; Jose Luis Fuster; Xavier Rialland; Céline Icher; Pierre Leblond; David Ashley; Giorgio Perilongo; Martin Elliott; Martin English; Niels Clausen; Jacques Grill Journal: J Neurooncol Date: 2013-03-04 Impact factor: 4.130
Authors: Amanda M Saratsis; Madhuri Kambhampati; Kendall Snyder; Sridevi Yadavilli; Joseph M Devaney; Brennan Harmon; Jordan Hall; Eric H Raabe; Ping An; Melanie Weingart; Brian R Rood; Suresh N Magge; Tobey J MacDonald; Roger J Packer; Javad Nazarian Journal: Acta Neuropathol Date: 2013-12-03 Impact factor: 17.088