LOCALIZATION OF ABERRANT MESSENGER-RNA OF EPIDERMAL GROWTH-FACTOR RECEPTOR (EGFR) IN MALIGNANT GLIOMA

Human gliomas occasionallly show rearrangements with deletions (exons II to VII) in the epidermal growth factor receptor (EGFR) gene, result ing in the expression of aberrant EGFR mRNA. This abnormality of EGFR gene expression is closely related to the malignancy of glioma. Howeve r this EGFR gene abnormality has not been demonstrated directly in the glioma cells themselves, as gliomas consist of heterogeneous tissue c omponents. In this study, we used in situ hybridization (ISH) to detec t aberrant EGFR mRNA in the tumor cells in 26 human gliomas and 19 hum an glioma xenografts. We used digoxigenin (DIG)- labeled antisense oli gonucleotide probes for ISH, which demonstrated aberrant EGFR mRNA in 2 of the 26 gliomas and in 3 of the 19 human glioma xenografts. ISH wi th an aberrant EGFR-specific probe (oligo-PA) revealed that EGFR mRNA was absent from multinucleated giant cells and from proliferating endo thelial cells, but this transcript was present in small glioma cells. Identical aberrant EGFR mRNA was confirmed in these glioma and human g lioma xenografts by Southern blotting, Northern blotting, and by rever se transcription-polymerase chain reaction (RT-PCR). These findings su ggest that small tumor. cells specifically express the aberrant EGFR m RNA in certain high grade gliomas.