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Reduced Expression of Mismatch Repair Genes Measured by Multiplex Reverse Transcription-Polymerase Chain Reaction in Human Gliomas¹

Departments of Epidemiology [Q. W., M. L. B., Y. G., L. C., J. C.], Thoracic and Head and Neck Medical Oncology [L. M., Y. F.], Pathology [J. M. B.], and Neuro-Oncology [W. K. A. Y., V. A. L., A. P. K.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Microsatellite instability (MIN) is frequently observed in hereditary nonpolyposis colon cancer and in other sporadic cancers including gliomas. Abnormalities in at least one of five mismatch repair (MMR) genes are implicated in the development of cancers in hereditary nonpolyposis colon cancer and the associated MIN. Using a newly developed multiplex reverse transcription-PCR assay, we evaluated the expression of the five known human MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and GTBP) in human gliomas by measuring simultaneously the relative levels of the transcripts. The ß-action gene was used as an internal control for RNA degradation and DNA contamination and as a reference for quantifying the levels of their transcripts. Of the 33 gliomas examined, 42% (14) had low expression of hMSH2 (at least 4–5-fold lower than normal mean), 21% (7) had low expression of hMLH1, and 18% (6) had low expression of hPMS1 compared with the expression in the lymphocytes from 13 normal individuals. Furthermore, six of the 33 (18%) tumor samples had decreased expression of more than one MMR gene. Two of these six patients with multiple gene abnormalities had second primary cancers, and an additional patient had multifocal gliomas. Further molecular analysis of available DNA samples indicated that one of five of those tumors with aberrant expression of MMR genes had MIN, as compared with none of five tumors with normal expression. These data suggest that reduced expression of MMR genes is frequent in human gliomas and that aberrant expression of more than one MMR gene may be associated with increased risk of second primary malignancies in glioma patients.

¹ This work was supported in part by a grant from the Charlotte Geyer Foundation (to M. L. B.), by NIH Grants CA70242 and CA70334 (to Q. W.), CA 70917 (to M. L. B.) and CA 55261 (to V. A. L.), and by National Cancer Institute Core Grant CA16672 to M. D. Andeson Cancer Center.

² To whom requests for reprints should be addressed, at Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 792-3020; Fax: (713) 792-0807; E-mail: qwei@request.mda.uth.tmc.edu.

Received 12/31/96. Accepted 3/20/97.

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