Abstract
BackgroundEpidermal growth factor receptor (EGFR) gene alterations and amplification are frequently reported in cases of glioblastoma (GBM). However, EGFR-activating mutations that confer proven sensitivity to tyrosine kinase inhibitors (TKIs) in lung cancer have not yet been reported in GBM.Case presentationUsing next-generation sequencing, array comparative genomic hybridization and droplet digital PCR, we identified the p.L861Q EGFR mutation in a case of GBM for the first time. The mutation was associated with gene amplification. L861Q may be a clinically valuable mutation because it is known to sensitize non-small-cell lung cancers to treatment with the second-generation EGFR TKI afatinib in particular. Furthermore, we used slice culture of the patient’s GBM explant to evaluate the tumour’s sensitivity to various EGFR-targeting drugs. Our results suggested that the tumour was not intrinsically sensitive to these drugs.ConclusionsOur results highlight (i) the value of comprehensive genomic analyses for identifying patient-specific, targetable alterations, and (ii) the need to combine genomic analyses with functional assays, such as tumour-derived slice cultures.
Highlights
Epidermal growth factor receptor (EGFR) gene alterations and amplification are frequently reported in cases of glioblastoma (GBM)
When comparing the results for samples from the same run, we found that the number of reads for each EGFR exon was much higher in the patient’s
We used panel-based Next-generation sequencing (NGS) and droplet-based digital PCR (ddPCR) to identify the exon 21 p.L861Q EGFR mutation for the first time in a case of IDH-wild type (WT) GBM. This somatic point mutation was associated with EGFR gene amplification, as revealed by NGS and Array comparative genomic hybridization (aCGH) experiments (Table 1 and Fig. 1)
Summary
Our results highlight (i) the value of comprehensive genomic analyses for identifying patient-specific, targetable alterations, and (ii) the need to combine genomic analyses with functional assays, such as tumour-derived slice cultures.
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