PTENIs a Target of Chromosome 10q Loss in Anaplastic Oligodendrogliomas and PTENAlterations Are Associated with Poor Prognosis

Allelic loss of 10q is a common genetic event in malignant gliomas, with three 10q tumor suppressor genes, ERCC6, PTEN, and DMBT1, putatively implicated in the most common type of malignant glioma, glioblastoma. Anaplastic oligodendroglioma, another type of malignant glioma, provides a unique opportunity to study the relevance of particular genetic alterations to chemosensitivity and survival. We therefore analyzed these three genes in 72 anaplastic oligodendrogliomas. Deletion mapping demonstrated 10q loss in 14 of 67 informative cases, with the PTENand DMBT1regions involved in all deletions but with the ERCC6locus spared in two cases. Seven tumors had PTENgene alterations; two had homozygous DMBT1deletions, but at least one reflected unmasking of a germline DMBT1deletion. No mutations were found in ERCC6exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTENalterations, but with unexpected short survival times. PTENgene alterations were not associated with poor therapeutic response in multivariate analysis, but were independently predictive of poor prognosis even after multivariate adjustment for both 10q and 1p loss. In anaplastic oligodendroglioma, therefore, PTENis a target of 10q loss, and PTENalterations are associated with poor prognosis, even in chemosensitive cases.