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PTEN/MMAC1 Mutations and EGFR Amplification in Glioblastomas¹

Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905

Loss of heterozygosity (LOH) from chromosome 10 is a hallmark of glioblastoma, the most malignant (grade IV) form of glioma. A candidate tumor suppressor gene, PTEN/MMAC1, that may be targeted for deletion in association with chromosome 10 LOH has recently been identified. Here we have investigated 63 glioblastomas for PTEN/MMAC1 alterations and identified DNA sequence changes that would affect the encoded protein in 17 (27%) tumors. Microsatellite analyses of normal-tumor DNA pairs were performed on 14 of these cases and revealed LOH at locations flanking and/or near PTEN/MMAC1 in all but 1 instance, suggesting that deletion of the remaining wild-type allele had occurred in the large majority of tumors with PTEN/MMAC1 mutations. Competitive PCR assays were developed to address the possible occurrence of PTEN/MMAC1 homozygous deletions in glioblastomas, and this analysis identified three samples having loss of both PTEN/MMAC1 alleles. EGFR amplification was determined to occur at similar frequencies among cases with or without PTEN/MMAC1 homozygous deletions or mutations, suggesting that a growth-promoting effect resulting from amplification-associated increases in epidermal growth factor receptor signaling is not necessarily dependent on the inactivation of PTEN/MMAC1.

¹ Supported by National Cancer Institute Grants CA-50905 (to R. B. J.) and CA-55728 (to C. D. J.).

² To whom requests for reprints should be addressed, at Mayo Clinic and Foundation, 200 First Street, S.W., Hilton Building, Room 820-D, Rochester, MN 55905. Phone: (507) 284-8989; Fax: (507) 266-5193; E-mail: james.charles@mayo.edu.

Received 8/14/97. Accepted 10/16/97.

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