NCOA4
Overview
NCOA4 (Nuclear Receptor Coactivator 4) is a nuclear receptor coactivator that facilitates androgen receptor transcriptional activity. It is also known as a ferritinophagy receptor involved in iron homeostasis through selective autophagy of ferritin. In thyroid cancer, NCOA4 is a fusion partner for RET, forming the RET/NCOA4 (also known as PTC3) fusion oncogene, which is a recurrent driver in papillary and poorly differentiated thyroid carcinomas.
Alterations observed in the corpus
- NCOA4 acts as a fusion partner for RET (RET-NCOA4 fusion) in 5 PDTC cases identified by targeted RNA-seq in a 341-gene panel study of poorly differentiated and anaplastic thyroid cancers; RET fusions (with CCDC6 or NCOA4) are among the gene fusions detected in PDTC but not ATC in this cohort PMID:26878173
- Partner in one NCOA4-RET fusion identified in MSS metastatic CRC; RET fusions are rare but potentially actionable events in this cohort PMID:29316426
Cancer types (linked)
- THPD (Poorly Differentiated Thyroid Carcinoma): RET-NCOA4 fusion is a recurrent driver fusion identified in PDTC; mutually exclusive with point mutations in RAS/BRAF. PMID:26878173
Co-occurrence and mutual exclusivity
- RET fusions (including RET-NCOA4) are mutually exclusive with BRAF V600E, RAS mutations, and ALK fusions in PDTC. PMID:26878173
Therapeutic relevance
- RET fusions in thyroid cancer are targetable by RET-selective inhibitors (e.g., selpercatinib, pralsetinib); this study identifies NCOA4 as a RET partner but does not evaluate RET-targeted therapy outcomes. PMID:26878173
Open questions
- Whether the frequency of RET-NCOA4 vs RET-CCDC6 fusions affects response to RET inhibitors in PDTC is not addressed in this study. PMID:26878173
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:29316426
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