Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer.

[en] Somatic mutations found within the tyrosine kinase domain (TKD) of the human epidermal growth factor (HER) family of receptors have been implicated in the development and progression of non-small cell lung cancer (NSCLC). However, no conclusive reports have described pathogenic mutations in kinase-impaired HER3. Here, we report a case of an advanced chemotherapy-resistant NSCLC, harboring a novel HER3V855A somatic mutation homologous to the EGFRL858Ractivating mutation. Co-expression of HER3V855A and wild-type HER2 enhances ligand-induced transformation of murine and human cell lines, while HER-targeted inhibitors potently suppress mutant HER3 activity. Consistent with these observations, in silico computational modeling predicts that mutant V855A alters the kinase domain and c-terminal end of the HER3 protein. Taken together, these findings provide a basis for the clinical exploration of targeted therapies in HER3 mutant NSCLC and by extrapolation, in other cancers that more frequently carry somatic HER3 mutations.

Disciplines :

Oncology

Author, co-author :

Umelo, Ijeoma ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Noeparast, Amir

Chen, Gang

Renard, Marleen

Geers, Caroline

Vansteenkiste, Johan

Giron, Philippe

De Wever, Olivier

Teugels, Erik

De Greve, Jacques

Language :

English

Title :

Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer.

Publication date :

January 2016

Journal title :

Oncotarget

eISSN :

1949-2553

Publisher :

Impact Journals, United States - New York

Volume :

Issue :

Pages :

3068-83

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 06 June 2016

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