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

BMC Cancer

Stephanie Trudel¹  Brigitte Gubler¹  Louison Collet¹  Bruno Chauffert¹  Lea Loriguet¹  Julie Dremaux¹  Mony Chenda Morisse¹  Antoine Galmiche¹  Henri Sevestre²  Christophe Attencourt²  Mathieu Boone³  Alexandre Coutte⁴ 

[1] EA4666, LNPC, Université de Picardie Jules Verne;Service d’Anatomie et de cytologie pathologiques, Centre Hospitalier Universitaire Amiens-Picardie;Service d’Oncologie médicale, Centre Hospitalier Universitaire Amiens-Picardie;Service d’Oncologie radiothérapique, Centre Hospitalier Universitaire Amiens-Picardie;

关键词: Glioblastoma;    EGFR;    Activating kinase mutation;    Tyrosine kinase inhibitors;    Afatinib;    Next-generation sequencing;   

DOI  :  10.1186/s12885-018-4873-9

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown