GRB7
Overview
GRB7 (Growth Factor Receptor Bound Protein 7) is an adaptor protein that binds directly to activated receptor tyrosine kinases, including ERBB2 (HER2). The GRB7 gene locus at 17q12 is co-amplified with ERBB2 in HER2-amplified cancers, and GRB7 is implicated in signaling downstream of HER2 through SH2-domain interactions. GRB7-ERBB2 gene fusions represent a rare structural variant class that retains the ERBB2 kinase domain and can drive oncogenic HER2 signaling.
Alterations observed in the corpus
- One patient in the SUMMIT basket trial harboured a GRB7-ERBB2 in-frame, kinase-retaining fusion as the qualifying ERBB2 alteration; this represents a rare structural variant class preserving HER2 kinase activity PMID:29420467
Cancer types (linked)
- BRCA: GRB7-ERBB2 in-frame fusion observed as a qualifying HER2 alteration in a breast cancer patient enrolled in the SUMMIT neratinib basket trial PMID:29420467
Co-occurrence and mutual exclusivity
- GRB7-ERBB2 fusion co-occurs with HER2 pathway activation; the fusion retains the ERBB2 kinase domain and is classified alongside other oncogenic ERBB2 alterations PMID:29420467
Therapeutic relevance
- The GRB7-ERBB2 kinase-retaining fusion was treated with neratinib (pan-HER TKI) as part of the SUMMIT basket trial targeting HER2-mutant/altered cancers PMID:29420467
Open questions
- Whether GRB7-ERBB2 fusions respond to neratinib at rates comparable to classical ERBB2 point mutations is not established from a single case.
Sources
This page was processed by crosslinker on 2026-05-15.