This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasaki, H. Articles by Louis, D. N. Search for Related Content PubMed PubMed Citation Articles by Sasaki, H. Articles by Louis, D. N.

(American Journal of Pathology. 2001;159:359-367.)
© 2001 American Society for Investigative Pathology

Regular Articles

PTEN Is a Target of Chromosome 10q Loss in Anaplastic Oligodendrogliomas and PTEN Alterations Are Associated with Poor Prognosis

Hikaru Sasaki^*, Magdalena C. Zlatescu, Rebecca A. Betensky, Yasushi Ino^*, J. Gregory Cairncross and David N. Louis^*

From the Molecular Neuro-Oncology Laboratory,^*
Department of Pathology and Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; the Department of Biostatistics,
Harvard School of Public Health, Boston, Massachusetts; and the Departments of Clinical Neurological Sciences and Oncology,
University of Western Ontario and London Regional Cancer Centre, London, Ontario, Canada

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 PTEN and DMBT1 regions involved in all deletions but with the ERCC6 locus spared in two cases. Seven tumors had PTEN gene alterations; two had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. No mutations were found in ERCC6 exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTEN alterations, but with unexpected short survival times. PTEN gene 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, PTEN is a target of 10q loss, and PTEN alterations are associated with poor prognosis, even in chemosensitive cases.

This article has been cited by other articles:

				I. Lavon, D. Zrihan, B. Zelikovitch, Y. Fellig, D. Fuchs, D. Soffer, and T. Siegal Longitudinal Assessment of Genetic and Epigenetic Markers in Oligodendrogliomas Clin. Cancer Res., March 1, 2007; 13(5): 1429 - 1437. [Abstract] [Full Text] [PDF]

				G. Mohapatra, R. A. Betensky, E. R. Miller, B. Carey, L. D. Gaumont, D. A. Engler, and D. N. Louis Glioma Test Array for Use with Formalin-Fixed, Paraffin-Embedded Tissue: Array Comparative Genomic Hybridization Correlates with Loss of Heterozygosity and Fluorescence in Situ Hybridization J. Mol. Diagn., May 1, 2006; 8(2): 268 - 276. [Abstract] [Full Text] [PDF]

				K. A. Jaeckle, K. V. Ballman, R. D. Rao, R. B. Jenkins, and J. C. Buckner Current Strategies in Treatment of Oligodendroglioma: Evolution of Molecular Signatures of Response J. Clin. Oncol., March 10, 2006; 24(8): 1246 - 1252. [Abstract] [Full Text] [PDF]

				A. Korshunov, R. Sycheva, and A. Golanov Molecular Stratification of Diagnostically Challenging High-Grade Gliomas Composed of Small Cells: The Utility of Fluorescence In situ Hybridization Clin. Cancer Res., December 1, 2004; 10(23): 7820 - 7826. [Abstract] [Full Text] [PDF]

				P. Leuraud, L. Taillandier, J. Medioni, L. Aguirre-Cruz, E. Criniere, Y. Marie, M. Kujas, J.-L. Golmard, A. Duprez, J.-Y. Delattre, et al. Distinct Responses of Xenografted Gliomas to Different Alkylating Agents Are Related to Histology and Genetic Alterations Cancer Res., July 1, 2004; 64(13): 4648 - 4653. [Abstract] [Full Text] [PDF]

				M. van den Bent, O.-L. Chinot, and J. G. Cairncross Recent developments in the molecular characterization and treatment of oligodendroglial tumors Neuro-oncol, April 1, 2003; 5(2): 128 - 138. [Abstract] [PDF]

				E. C. Burton, K. R. Lamborn, B. G. Feuerstein, M. Prados, J. Scott, P. Forsyth, S. Passe, R. B. Jenkins, and K. D. Aldape Genetic Aberrations Defined by Comparative Genomic Hybridization Distinguish Long-Term from Typical Survivors of Glioblastoma Cancer Res., November 1, 2002; 62(21): 6205 - 6210. [Abstract] [Full Text] [PDF]

				L. Del Valle, S. Enam, C. Lara, C. Ortiz-Hidalgo, C. D. Katsetos, and K. Khalili Detection of JC Polyomavirus DNA Sequences and Cellular Localization of T-Antigen and Agnoprotein in Oligodendrogliomas Clin. Cancer Res., November 1, 2002; 8(11): 3332 - 3340. [Abstract] [Full Text] [PDF]

				C. B. Knobbe, A. Merlo, and G. Reifenberger Pten signaling in gliomas Neuro-oncol, July 1, 2002; 4(3): 196 - 211. [Abstract] [PDF]

				H. Sasaki, R. A. Betensky, J. G. Cairncross, and D. N. Louis DMBT1 Polymorphisms: Relationship to Malignant Glioma Tumorigenesis Cancer Res., March 1, 2002; 62(6): 1790 - 1796. [Abstract] [Full Text] [PDF]