Oncotarget

Clinical Research Papers:

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 and Caterina Giannini

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Oncotarget. 2015; 6:30295-30305. https://doi.org/10.18632/oncotarget.4497

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Abstract

Heather E. Leeper1, Alissa A. Caron2, Paul A. Decker3, Robert B. Jenkins5, Daniel H. Lachance4, Caterina Giannini5

1Neuro-Oncology, Advocate Medical Group, Park Ridge, IL 60068, USA

2Experimental Pathology, Mayo Clinic SW, Rochester, MN 55905, USA

3Biomedical Statistics and Informatics, Mayo Clinic SW, Rochester, MN 55905, USA

4Neurology, Mayo Clinic SW, Rochester, MN 55905, USA

5Anatomic Pathology, Mayo Clinic SW, Rochester, MN 55905, USA

Correspondence to:

Caterina Giannini, e-mail: giannini.caterina@mayo.edu

Keywords: diffuse gliomas, WHO grade II, IDH mutation, ATRX, 1p19q codeletion

Received: March 12, 2015     Accepted: June 22, 2015     Published: July 03, 2015

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.


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