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| Gene | ERBB3 |
| Variant | G284R |
| Impact List | missense |
| Protein Effect | unknown |
| Gene Variant Descriptions | ERBB3 (HER3) G284R lies within the extracellular domain of the Erbb3 (Her3) protein (UniProt.org). G284R results in increased phosphorylation of Akt and Erk, as well as oncogenic transformation of Erbb2 (Her2)-expressing cells relative to wild-type Erbb3 (Her3) (PMID: 23680147), leads to increased cell proliferation in Erbb2 (Her2)-overexpressing cells in culture (PMID: 29963236), and results in a modest increase in Erbb2 phosphorylation and IL3-independent growth when expressed with ERBB2 (HER2) V956R in culture (PMID: 38806620), but has not been individually characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown. |
| Associated Drug Resistance | |
| Category Variants Paths |
ERBB3 mutant ERBB3 G284R |
| Transcript | NM_001982.4 |
| gDNA | chr12:g.56088138G>A |
| cDNA | c.850G>A |
| Protein | p.G284R |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_001982.4 | chr12:g.56088138G>A | c.850G>A | p.G284R | RefSeq | GRCh38/hg38 |
| NM_001982.3 | chr12:g.56088138G>A | c.850G>A | p.G284R | RefSeq | GRCh38/hg38 |
| NM_001982 | chr12:g.56088138G>A | c.850G>A | p.G284R | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ERBB3 G284R | Advanced Solid Tumor | sensitive | Lapatinib | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) inhibited proliferation and colony formation in transformed cell lines expressing ERBB3 (HER3) G284R (PMID: 23680147). | 23680147 |
| ERBB3 G284R | Advanced Solid Tumor | sensitive | Duligotuzumab | Preclinical | Actionable | In a preclinical study, MEHD7945A inhibited proliferation and colony formation in transformed cell lines expressing ERBB3 (HER3) G284R (PMID: 23680147). | 23680147 |
| ERBB3 G284R | Advanced Solid Tumor | sensitive | Trastuzumab | Preclinical | Actionable | In a preclinical study, Herceptin (trastuzumab) inhibited proliferation and colony formation in transformed cell lines expressing ERBB3 (HER3) G284R (PMID: 23680147). | 23680147 |
| ERBB3 G284R | Advanced Solid Tumor | sensitive | Pertuzumab | Preclinical | Actionable | In a preclinical study, Perjeta (pertuzumab) inhibited proliferation and colony formation in transformed cell lines expressing ERBB3 (HER3) G284R (PMID: 23680147). | 23680147 |
| ERBB3 G284R | Advanced Solid Tumor | resistant | Cetuximab | Preclinical | Actionable | In a preclinical study, transformed cell lines expressing ERBB3 (HER3) G284R demonstrated resistance to treatment with Erbitux (cetuximab) (PMID: 23680147). | 23680147 |
| ERBB3 G284R | Advanced Solid Tumor | sensitive | Pictilisib | Preclinical | Actionable | In a preclinical study, the PI3K inhibitor GDC-0941 inhibited proliferation and colony formation in transformed cell lines expressing ERBB3 (HER3) G284R (PMID: 23680147). | 23680147 |
| ERBB3 G284R | Advanced Solid Tumor | sensitive | Mirdametinib + Pictilisib | Preclinical | Actionable | In a preclinical study, the combination of GDC-0941 and Gomekli (mirdametinib) inhibited proliferation and colony formation in transformed cell lines expressing ERBB3 (HER3) G284R (PMID: 23680147). | 23680147 |
| ERBB3 G284R | transitional cell carcinoma | sensitive | Afatinib | Case Reports/Case Series | Actionable | In a Phase II trial, a patient with urothelial carcinioma harboring ERBB3 G284R demonstrated stable disease for 7 months when treated with Gilotrif (afatinib) (J Clin Oncol 33, 2015 (suppl 7; abstr 312)). | detail... |
| ERBB3 G284R | urinary bladder cancer | sensitive | Afatinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, a patient with ERBB3 G284R mutant urothelial carcinoma had improved progression free survival when treated with Gilotrif (afatinib), and median PFS was 6.6 months for patients with ERBB2 or ERBB3 alterations relative to 1.4 months for patients lacking alterations (PMID: 27044931). | 27044931 |
| ERBB3 G284R | breast cancer | predicted - sensitive | Lapatinib + Trastuzumab | Case Reports/Case Series | Actionable | In a clinical case study, the combination treatment of Herceptin (trastuzumab) and Tykerb (lapatinib) in a patient with breast cancer harboring ERBB3 (HER3) G284R resulted in antitumor efficacy, demonstrating a complete metabolic response after day 14 of treatment, a partial response after 8 weeks of treatment, and no clinical evidence of disease after 40 weeks of treatment (PMID: 25953157). | 25953157 |
| ERBB3 G284R | breast cancer | sensitive | Patritumab deruxtecan | Preclinical - Cell culture | Actionable | In a preclinical study, Patritumab deruxtecan (U3-1402) treatment inhibited growth of a breast cancer cell line expressing ERBB3 (HER3) G284R in culture (PMID: 35503762). | 35503762 |
| ERBB3 G284R | Her2-receptor positive breast cancer | predicted - sensitive | Neratinib + Palbociclib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with the combination of Nerlynx (neratinib) and Ibrance (palbociclib) resulted in an objective response rate of 16.7% (5/30, all partial responses) and clinical benefit rate of 26.7% in patients with advanced solid tumors harboring HER alterations, including a partial response in a patient with ESR1-positive, ERBB2 (HER2)-positive breast cancer harboring ERBB3 G284R (PMID: 41223631; NCT03065387). | 41223631 |