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Department of Neuropathology and Center for Biological and Medical Research, Heinrich-Heine-University, D-40225 Düsseldorf, Germany [J. B., J. M. J. L. C., M. W., G. T., G. R.]; Abteilung Organisation Komplexer Genome, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany [R. G. W., P. L.]; and Ludwig Institute for Cancer Research and Institute for Pathology and Oncology, Karolinska Hospital, S-17176 Stockholm, Sweden [V. P. C.]
The PTEN (MMAC1) gene, which has been identified as a tumor suppressor gene at 10q23.3, is mutated in multiple malignant tumors, including glioblastomas [J. Li et al., Science (Washington DC), 275: 1943–1947, 1997; P. A. Steck et al., Nat. Genet., 15: 356–362, 1997]. Among tumors of the central nervous system, loss of 10q is not restricted to glioblastomas but is also common in atypical and anaplastic meningiomas. Therefore, we have investigated 36 glioblastomas and 34 meningiomas (2 benign, 17 atypical, and 15 anaplastic meningiomas) for loss on 10q, as well as deletion, mutation, and expression of PTEN. Analysis of eight microsatellites from 10q revealed loss of heterozygosity (LOH) in 25 of 36 glioblastomas (69%). Twenty-three of three tumors demonstrated LOH at all informative loci. Two glioblastomas showed LOH restricted to markers located distally to PTEN, with breakpoints mapping telomeric to D10S541 and D10S185. One glioblastoma demonstrated evidence of homozygous deletion of PTEN by differential PCR analysis. PTEN mutations were detected in 9 of 36 glioblastomas (25%). Seven of these tumors showed LOH at all informative loci from 10q, indicating complete loss of wild-type PTEN. Although loss of 10q was detected by comparative genomic hybridization and/or LOH analysis in 14 of the 34 meningiomas investigated (41%), none of these tumors showed evidence of PTEN mutations or homozygous gene deletions. Our findings corroborate that PTEN is inactivated in a subset of glioblastomas. However, the lack of detectable PTEN alterations in a considerable fraction of glioblastomas and all meningiomas with 10q loss strongly supports the hypothesis that at least one additional tumor suppressor gene is located on 10q.
1 This work was supported by Deutsche Forschungsgemeinschaft Grant Re 938/2-2, Deutsche Krebshilfe Grants 10-0976-Re1 and 10-1124-Li1, the Schäfersnolte Foundation, and the Swedish Cancer Fund. J. B. is a postdoctoral fellow supported by the Gertrud-Reemtsma-Stiftung.
2 The first three authors contributed equally to this work.
3 To whom requests for reprints should be addressed, at Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse, D-40225 Düsseldorf, Germany. Phone: 49-211-8118662; Fax: 49-211-8117804; E-mail: reifenb@rz.uni-duesseldorf.de.
Received 8/26/97. Accepted 11/12/97.
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