MUTATION OF THE PTEN (MMAC1) TUMOR-SUPPRESSOR GENE IN A SUBSET OF GLIOBLASTOMAS BUT NOT IN MENINGIOMAS WITH LOSS OF CHROMOSOME ARM 10Q

The PTEN (MMAC1) gene, which has been identified as a tumor suppressor gene at 10q23.3, is mutated in multiple malignant tumors, including g lioblastomas [J. Li et al., Science (Washington DC), 275: 1943-1947, 1 997; 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 gliob lastomas but is also common in atypical and anaplastic meningiomas. Th erefore, we have investigated 36 glioblastomas and 34 meningiomas (2 b enign, 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 these tumors demonstrated L OH 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 homo zygous deletion of PTEN by differential PCR analysis, PTEN mutations w ere detected in 9 of 36 glioblastomas (25%). Seven of these tumors sho wed LOH at all informative loci from 10q, indicating complete loss of wild-type PTEN. Although loss of 10q was detected by comparative genom ic hybridization and/or LOH analysis in 14 of the 34 meningiomas inves tigated (41%), none of these tumors showed evidence of PTEN mutations or homozygous gene deletions, Our findings corroborate that PTEN is in activated in a subset of glioblastomas. However, the lack of detectabl e PTEN alterations in a considerable fraction of glioblastomas and all meningiomas with 10q loss strongly supports the hypothesis that at le ast one additional tumor suppressor gene is located on 10q.