EGFR Pathway Expression Persists in Recurrent Glioblastoma Independent of Amplification Status

Glioblastoma mortality is driven by tumour progression or recurrence despite administering a therapeutic arsenal consisting of surgical resection, radiation, and alkylating chemotherapy. The genetic changes underlying tumour progression and chemotherapy resistance are poorly understood. In this stud...

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Bibliographic Details
Published in:Cancers 2023-01, Vol.15 (3), p.670
Main Authors: Dhawan, Andrew, Manem, Venkata S K, Yeaney, Gabrielle, Lathia, Justin D, Ahluwalia, Manmeet S
Format: Article
Language:English
Subjects:
Biopsy
Brain cancer
Chemoresistance
Chemotherapy
Chromosomes
Consortia
Development and progression
Epidermal growth factor receptors
Gene amplification
Gene expression
Genetic aspects
Genomes
Glioblastoma
Glioblastoma multiforme
Health aspects
Patients
Tumors
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Summary:Glioblastoma mortality is driven by tumour progression or recurrence despite administering a therapeutic arsenal consisting of surgical resection, radiation, and alkylating chemotherapy. The genetic changes underlying tumour progression and chemotherapy resistance are poorly understood. In this study, we sought to define the relationship between EGFR amplification status, EGFR mRNA expression, and EGFR pathway activity. We compared RNA-sequencing data from matched primary and recurrent tumour samples ( = 40 patients, 20 with EGFR amplification). In the setting of glioblastoma recurrence, the EGFR pathway was overexpressed regardless of EGFR-amplification status, suggesting a common genomic endpoint in recurrent glioblastoma, although EGFR amplification did associate with higher EGFR mRNA expression. Three of forty patients in the study cohort had EGFR-amplified tumours and received targeted EGFR therapy. Their molecular subtypes and clinical outcomes did not significantly differ from patients who received conventional chemotherapy. Our findings suggest that while the EGFR amplification may confer a unique molecular profile in primary glioblastoma, pathway analysis reveals upregulation of the EGFR pathway in recurrence, regardless of amplification status. As such, the EGFR pathway may be a key mediator of glioblastoma progression.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15030670