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Ref Type Journal Article
PMID (26689995)
Authors Umelo I, Noeparast A, Chen G, Renard M, Geers C, Vansteenkiste J, Giron P, De Wever O, Teugels E, De Grève J
Title Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer.
Journal Vol Issue Date Pages Journal Short Title
Oncotarget 7 3 2016 Jan 19 3068-83 Oncotarget
URL
Abstract Text 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 HER3(V855A) somatic mutation homologous to the EGFR(L858R)activating mutation. Co-expression of HER3(V855A) 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.

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Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ERBB3 V855A missense gain of function ERBB3 (HER3) V855A lies within the activation loop of the Erbb3 (Her3) protein (PMID: 26689995). V855A confers a gain of function to Erbb3 (Her3), as indicated by increased NRG1-beta induced cell growth in the presence of wild-type ERBB2 (HER2), increased interaction with ERBB2 (HER2), and increased ERBB2 (HER2) trans-phosphorylation in cell culture (PMID: 26689995).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References