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Combined 1p/19q Loss in Oligodendroglial Tumors: Predictive or Prognostic Biomarker?

Authors' Affiliations: ¹ Department of General Neurology, University of Tübingen, Tübingen, Germany; ² Institute of Medicinal Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; ³ Institute of Neuropathology, Charité, Universitätsmedizin Berlin, Berlin, Germany; ⁴ Departments of Neurosurgery and ⁵ Neuropathology, University of Bonn, Bonn, Germany; ⁶ Department of Neurosurgery, University of Hamburg, Hamburg, Germany; ⁷ Department of Neurosurgery, University of Munich, Munich, Germany; ⁸ Department of Neurosurgery, University of Dresden, Dresden, Germany; and ⁹ Department of Stereotactic Neurosurgery, University of Freiburg, Freiburg, Germany

Requests for reprints: Michael Weller, Department of General Neurology, University of Tübingen Medical School, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany. Phone: 49-7071-29-82049; Fax: 49-7071-29-5260; E-mail: michael.weller{at}uni-tuebingen.de.

Purpose: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy.

Experimental Design: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation–dependent probe amplification.

Results: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender.

Conclusions: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.

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