In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. LB-203-LB-203
Abstract:
Medulloblastoma is a highly malignant pediatric brain tumor currently treated with a combination of surgery, radiation, and non-specific chemotherapy, posing a significant threat to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma and identified four distinct molecular subgroups. Group 3 and Group 4 subgroup medulloblastomas account for the majority of pediatric cases, yet, oncogenic drivers for these subtypes remain poorly understood. Here we report a series of prevalent, highly disparate genomic structural rearrangements, restricted to Groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto- oncogenes, GFI1 & GFI1B. Diverse mechanisms of structural variation activate GFI1/GFI1B expression through relocation of their coding sequences to genomic regions of transcriptionally active chromatin. Moreover, Gfi1 and Gfi1b each cooperate with Myc, an important oncogene in Group 3 medulloblastomas, to drive tumor initiation in mice. These data reveal GFI1 and GFI1B as novel medulloblastoma oncogenes, warranting their prioritization for molecularly targeted therapy of a marked proportion of Group 3 and Group 4 patients. Citation Format: Catherine Lee, Paul A. Northcott, Thomas Zichner, Peter Lichter, Jan O. Korbel, Stefan M. Pfister, Robert J. Wechsler-Reya. Structural variants shuffle chromatin to activate GFI1 family oncogenes in medulloblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-203. doi:10.1158/1538-7445.AM2014-LB-203
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-LB-203
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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