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

• Published in: BMC cancer Vol. 18; no. 1; p. 964
• Main Authors: Loriguet, Lea, Morisse, Mony Chenda, Dremaux, Julie, Collet, Louison, Attencourt, Christophe, Coutte, Alexandre, Boone, Mathieu, Sevestre, Henri, Galmiche, Antoine, Gubler, Brigitte, Chauffert, Bruno, Trudel, Stephanie
• Format: Journal Article
• Language: English
• Published: England BioMed Central 11.10.2018; BMC
• Subjects: Activating kinase mutation; Afatinib; Aged; Brain cancer; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - therapy; Brain research; Cancer therapies; Case Report; Cell culture; Colorectal cancer; Comparative Genomic Hybridization; Deoxyribonucleic acid; DNA; DNA methylation; Drug delivery; EGFR; Enzyme Activation - genetics; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Female; Gene amplification; Genomes; Genomic analysis; Glioblastoma; Glioblastoma - enzymology; Glioblastoma - genetics; Glioblastoma - therapy; Humans; Kinases; Life Sciences; Lung cancer; Medical research; Metastasis; Mutation; Next-generation sequencing; Patients; Plasma; Polymerase Chain Reaction; Protein Kinase Inhibitors - pharmacology; Protein-tyrosine kinase; Radiation therapy; Sequence Analysis, DNA; Software; Tumor Cells, Cultured; Tumors; Tyrosine kinase inhibitors; Next-generation sequencing; Afatinib; Activating kinase mutation; Glioblastoma; Tumour-derived slice cultures; EGFR; Tyrosine kinase inhibitors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4873-9

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. 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. 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.