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Combining genomic analyses with tumour-derived slice cultures for the characterization of an EGFR-activating kinase mutation in a case of glioblastoma

Abstract : Background: Epidermal 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 presentation: Using 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. Conclusions: 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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https://hal-u-picardie.archives-ouvertes.fr/hal-03598674
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Soumis le : samedi 5 mars 2022 - 17:54:50
Dernière modification le : jeudi 25 août 2022 - 17:20:32

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Lea Loriguet, Mony Chenda Morisse, Julie Dremaux, Louison Collet, Christophe Attencourt, et al.. Combining genomic analyses with tumour-derived slice cultures for the characterization of an EGFR-activating kinase mutation in a case of glioblastoma. BMC Cancer, BioMed Central, 2018, 18, ⟨10.1186/s12885-018-4873-9⟩. ⟨hal-03598674⟩

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