IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas

Heather E. Leeper, Alissa A. Caron, Paul A. Decker, Robert B. Jenkins, Daniel H. Lachance, Caterina Giannini

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Background: Epigenetic, genetic, and molecular studies have identified several diagnostic and prognostic markers in diffuse gliomas. Their importance for evaluating WHO grade II gliomas has yet to be specifically delineated. Methods: We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003-2012). Results: IDHmut was found in 141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors (p = 0.003). All codeleted tumors (n = 66) were IDHmut. Four subgroups were identified: IDHmut-codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt, 9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different (p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared to the remaining 3 groups (p = 0.025). Survival by histology was not significant. Overall (OS), but not progression-free (PFS), survival was significantly longer with gross total resection vs. biopsy only (p = 0.042). Outcomes for patients with subtotal resection were not significantly different from those with biopsy only. Among these uniformly treated patients, OS far exceeds PFS, particularly in those with 1p/19q codeletion. Conclusions: For WHO grade II diffuse glioma, molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately predicts outcome and should be incorporated in the neuropathologic evaluation.

Original languageEnglish (US)
Pages (from-to)30295-30305
Number of pages11
JournalOncotarget
Volume6
Issue number30
DOIs
StatePublished - 2015

Keywords

  • 1p19q codeletion
  • ATRX
  • Diffuse gliomas
  • IDH mutation
  • WHO grade II

ASJC Scopus subject areas

  • Oncology

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