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

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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

Fingerprint

Glioma
Mutation
Survival
Biopsy
Oligodendroglioma
Astrocytoma
Epigenomics
Disease-Free Survival
Molecular Biology
Neoplasms
Histology

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. / Leeper, Heather E.; Caron, Alissa A.; Decker, Paul A.; Jenkins, Robert Brian; Lachance, Daniel H; Giannini, Caterina.

In: Oncotarget, Vol. 6, No. 30, 2015, p. 30295-30305.

Research output: Contribution to journalArticle

Leeper, Heather E. ; Caron, Alissa A. ; Decker, Paul A. ; Jenkins, Robert Brian ; Lachance, Daniel H ; Giannini, Caterina. / IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. In: Oncotarget. 2015 ; Vol. 6, No. 30. pp. 30295-30305.
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AU - Leeper, Heather E.

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AU - Decker, Paul A.

AU - Jenkins, Robert Brian

AU - Lachance, Daniel H

AU - Giannini, Caterina

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AB - 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.

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