The genetic landscape of anaplastic astrocytoma.
Journal Article (Journal Article)
Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type, we sequenced the exome of a cohort of A3s (n=16). For comparison and to illuminate the genomic landscape of other glioma subtypes, we also included in our study diffuse astrocytoma WHO grade II (A2, n=7), oligoastrocytoma WHO grade II (OA2, n=2), anaplastic oligoastrocytoma WHO grade III (OA3, n=4), and GBM (n=28). Exome sequencing of A3s identified frequent mutations in IDH1 (75%, 12/16), ATRX (63%, 10/16), and TP53 (82%, 13/16). In contrast, the majority of GBMs (75%, 21/28) did not contain IDH1 or ATRX mutations, and displayed a distinct spectrum of mutations. Finally, our study also identified novel genes that were not previously linked to this tumor type. In particular, we found mutations in Notch pathway genes (NOTCH1, NOTCH2, NOTCH4, NOTCH2NL), including a recurrent NOTCH1-A465Tmutation, in 31% (5/16) of A3s. This study suggests genetic signatures will be useful for the classification of gliomas.
Full Text
Duke Authors
- Bigner, Darell Doty
- Friedman, Allan Howard
- Friedman, Henry Seth
- He, Yiping
- McLendon, Roger Edwin
- Pirozzi, Christopher
- Reitman, Zachary James
Cited Authors
- Killela, PJ; Pirozzi, CJ; Reitman, ZJ; Jones, S; Rasheed, BA; Lipp, E; Friedman, H; Friedman, AH; He, Y; McLendon, RE; Bigner, DD; Yan, H
Published Date
- March 30, 2014
Published In
Volume / Issue
- 5 / 6
Start / End Page
- 1452 - 1457
PubMed ID
- 24140581
Pubmed Central ID
- PMC4039223
Electronic International Standard Serial Number (EISSN)
- 1949-2553
Digital Object Identifier (DOI)
- 10.18632/oncotarget.1505
Language
- eng
Conference Location
- United States