ERRFI1
Overview
ERRFI1 (also known as MIG6, Mitogen-Inducible Gene 6) encodes an adapter protein that negatively regulates ErbB receptor tyrosine kinases, particularly EGFR. By binding to and inhibiting EGFR, ERRFI1 acts as a tumor suppressor. Loss-of-function mutations or downregulation of ERRFI1 can result in sustained EGFR signaling, and ERRFI1 alterations have been proposed to explain erlotinib sensitivity in some EGFR wild-type lung adenocarcinoma patients.
Alterations observed in the corpus
- ERRFI1 A143D missense identified in 1 patient with unknown molecular driver (UMD) who derived erlotinib clinical benefit despite the absence of an EGFR mutation; ERRFI1 mutations identified in 6 patients (0.7%) total across the cohort, with 4 cases carrying co-occurring higher-level alterations (2 with EGFR exon 19 deletion; 2 with KRAS G12) PMID:28336552
Cancer types (linked)
- Lung adenocarcinoma (LUAD): ERRFI1 mutations present in 0.7% of a clinical sequencing cohort; associated with erlotinib sensitivity in one UMD case PMID:28336552
Co-occurrence and mutual exclusivity
- ERRFI1 mutations observed co-occurring with EGFR exon 19 deletions (n=2) and KRAS G12 mutations (n=2) in the same sequencing cohort PMID:28336552
Therapeutic relevance
- ERRFI1 A143D associated with erlotinib benefit in the absence of a canonical EGFR sensitizing mutation, suggesting ERRFI1 loss-of-function may confer EGFR pathway dependence actionable with EGFR TKIs PMID:28336552
Open questions
- The mechanistic basis for ERRFI1 mutation-driven erlotinib sensitivity in EGFR wild-type tumors remains to be prospectively validated in larger cohorts PMID:28336552
Sources
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