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Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors
D K Moscatello1, M Holgado-Madruga, A K Godwin
1Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
The epidermal growth factor receptor has received much interest as a target for various antineoplastic agents, but a complication is that many normal tissues also express this receptor. We have previously identified in human glial tumors an 801-bp in-frame deletion within the epidermal growth factor receptor gene that created a novel epitope at the junction. By using Western blot assays with a mutant-specific antibody as a rapid and sensitive means for detecting this alteration in primary human tumors, it was found that 57% (26 of 46) of high-grade and 86% (6 of 7) of low-grade glial tumors, but not normal brain, express this protein. This altered receptor was also present in 66% (4 of 6) of pediatric gliomas and 86% (6 of 7) of medulloblastomas, 78% (21 of 27) of breast carcinomas, and 73% (24 of 32) of ovarian carcinomas. The fact that this receptor is frequently found in tumors but not in normal tissue makes it an attractive candidate for various antitumor strategies.
Insights
A novel epidermal growth factor receptor (EGFR) alteration is frequently detected in various tumors, including glial tumors, breast, and ovarian carcinomas. This EGFR mutation is absent in normal brain tissue, making it a promising target for cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) is a target for antineoplastic agents.
- A challenge is that normal tissues also express EGFR, limiting targeted therapy efficacy.
- A specific 801-bp in-frame deletion in the EGFR gene creates a novel epitope in human glial tumors.
Purpose of the Study:
- To develop a rapid and sensitive method for detecting the EGFR alteration in primary human tumors.
- To assess the prevalence of this altered EGFR in various cancer types and normal brain tissue.
- To evaluate the potential of this altered EGFR as a therapeutic target.
Main Methods:
- Western blot assays utilizing a mutant-specific antibody.
- Analysis of primary human tumor samples, including glial tumors, pediatric gliomas, medulloblastomas, breast carcinomas, and ovarian carcinomas.
- Comparison with normal brain tissue samples.
Main Results:
- The mutant-specific antibody successfully detected the altered EGFR protein.
- The altered EGFR was found in 57% of high-grade and 86% of low-grade glial tumors, but not in normal brain.
- High frequencies of the altered EGFR were also observed in pediatric gliomas (66%), medulloblastomas (86%), breast carcinomas (78%), and ovarian carcinomas (73%).
Conclusions:
- The identified EGFR alteration is frequently present in a wide range of tumors.
- The absence of this altered EGFR in normal tissues suggests its specificity as a tumor marker.
- This frequently occurring, tumor-specific EGFR alteration represents a promising candidate for novel antitumor strategies.