Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Subgroup specific somatic copy number aberrations in the medulloblastoma genome [mRNA]

ABSTRACT: Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples. Total RNA was extracted from primary medulloblastoma samples and hybridized to Affymetrix Human Gene 1.1 ST Arrays (24-Array Plates) according to the manufacturer's instructions.

ORGANISM(S): Homo sapiens

SUBMITTER: Paul Northcott

PROVIDER: E-GEOD-37382 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Northcott Paul A PA Shih David J H DJ Peacock John J Garzia Livia L Morrissy A Sorana AS Zichner Thomas T Stütz Adrian M AM Korshunov Andrey A Reimand Jüri J Schumacher Steven E SE Beroukhim Rameen R Ellison David W DW Marshall Christian R CR Lionel Anath C AC Mack Stephen S Dubuc Adrian A Yao Yuan Y Ramaswamy Vijay V Luu Betty B Rolider Adi A Cavalli Florence M G FM Wang Xin X Remke Marc M Wu Xiaochong X Chiu Readman Y B RY Chu Andy A Chuah Eric E Corbett Richard D RD Hoad Gemma R GR Jackman Shaun D SD Li Yisu Y Lo Allan A Mungall Karen L KL Nip Ka Ming KM Qian Jenny Q JQ Raymond Anthony G J AG Thiessen Nina T NT Varhol Richard J RJ Birol Inanc I Moore Richard A RA Mungall Andrew J AJ Holt Robert R Kawauchi Daisuke D Roussel Martine F MF Kool Marcel M Jones David T W DT Witt Hendrick H Fernandez-L Africa A Kenney Anna M AM Wechsler-Reya Robert J RJ Dirks Peter P Aviv Tzvi T Grajkowska Wieslawa A WA Perek-Polnik Marta M Haberler Christine C CC Delattre Olivier O Reynaud Stéphanie S SS Doz François F FF Pernet-Fattet Sarah S SS Cho Byung-Kyu BK Kim Seung-Ki SK Wang Kyu-Chang KC Scheurlen Wolfram W Eberhart Charles G CG Fèvre-Montange Michelle M Jouvet Anne A Pollack Ian F IF Fan Xing X Muraszko Karin M KM Gillespie G Yancey GY Di Rocco Concezio C Massimi Luca L Michiels Erna M C EM Kloosterhof Nanne K NK French Pim J PJ Kros Johan M JM Olson James M JM Ellenbogen Richard G RG Zitterbart Karel K Kren Leos L Thompson Reid C RC Cooper Michael K MK Lach Boleslaw B McLendon Roger E RE Bigner Darell D DD Fontebasso Adam A Albrecht Steffen S Jabado Nada N Lindsey Janet C JC Bailey Simon S Gupta Nalin N Weiss William A WA Bognár László L Klekner Almos A Van Meter Timothy E TE Kumabe Toshihiro T Tominaga Teiji T Elbabaa Samer K SK Leonard Jeffrey R JR Rubin Joshua B JB Liau Linda M LM Van Meir Erwin G EG Fouladi Maryam M Nakamura Hideo H Cinalli Giuseppe G Garami Miklós M Hauser Peter P Saad Ali G AG Iolascon Achille A Jung Shin S Carlotti Carlos G CG Vibhakar Rajeev R Ra Young Shin YS Robinson Shenandoah S Zollo Massimo M Faria Claudia C CC Chan Jennifer A JA Levy Michael L ML Sorensen Poul H B PH Meyerson Matthew M Pomeroy Scott L SL Cho Yoon-Jae YJ Bader Gary D GD Tabori Uri U Hawkins Cynthia E CE Bouffet Eric E Scherer Stephen W SW Rutka James T JT Malkin David D Clifford Steven C SC Jones Steven J M SJ Korbel Jan O JO Pfister Stefan M SM Marra Marco A MA Taylor Michael D MD

Nature 20120801 7409

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastoma ...[more]

PMID: 22832581

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Project description:Recent genomic approaches have suggested the existence of multiple distinct subtypes of medulloblastoma. We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups. We determined gene expression profiles and DNA copy number aberrations for 103 primary medulloblastomas. Bioinformatic tools were used for class discovery of medulloblastoma subgroups based on the most informative genes in the dataset. Immunohistochemistry for subgroup-specific ‘signature’ genes was used to determine subgroup affiliation for 294 non-overlapping medulloblastomas on two independent tissue microarrays (TMAs). Multiple unsupervised analyses of transcriptional profiles identified four distinct, non-overlapping molecular variants: WNT, SHH, Group C, and Group D. Supervised analysis of these four subgroups revealed significant subgroup-specific demographics, histology, metastatic status, and DNA copy number aberrations. Immunohistochemistry for DKK1 (WNT), SFRP1 (SHH), NPR3 (Group C), and KCNA1 (Group D) could reliably and uniquely classify formalin fixed medulloblastomas in ~98% of cases. Group C patients (NPR3 +ve tumors) exhibited a significantly diminished progression free and overall survival irrespective of their metastatic status. Our integrative genomics approach to a large cohort of medulloblastomas has identified four disparate subgroups with distinct demographics, clinical presentation, transcriptional profiles, genetic abnormalities, and clinical outcome. Medulloblastomas can be reliably assigned to subgroups through immunohistochemistry, thereby making medulloblastoma sub-classification widely available. Future research on medulloblastoma and the development of clinical trials should take into consideration these four distinct types of medulloblastoma. A total of 103 primary medulloblastoma specimens were profiled by Affymetrix exon array and gene-level analysis was performed.

Dataset Information

Subgroup specific somatic copy number aberrations in the medulloblastoma genome [mRNA]

Publications

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Similar Datasets

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