TNIP2
Overview
TNIP2 (TNFAIP3-interacting protein 2) is a scaffold protein involved in NF-kB signaling regulation. In cancer genomics, it has been identified as a fusion partner in activating FGFR3 gene fusions, which arise in urothelial tumors and drive receptor tyrosine kinase signaling through preservation of the FGFR3 kinase domain.
Alterations observed in the corpus
- FGFR3-TNIP2 fusion identified in 1 low-grade Ta non-muscle-invasive bladder cancer (NMIBC) tumor; predicted activating with an in-frame FGFR3 kinase domain; detected by MSK-IMPACT targeted NGS panel (n=105 NMIBC tumors) PMID:28583311
Cancer types (linked)
- BLCA — FGFR3-TNIP2 fusion observed in NMIBC (low-grade Ta); part of a broader pattern of FGFR3 fusions (4 total detected) that, together with FGFR3 hotspot mutations, characterize a targetable subset of bladder cancer PMID:28583311
Co-occurrence and mutual exclusivity
- FGFR3-TNIP2 fusion falls within the FGFR3-altered group, which is mutually exclusive with ERBB2 alterations in high-grade NMIBC PMID:28583311
Therapeutic relevance
- FGFR3 fusions including FGFR3-TNIP2 represent potential targets for FGFR3 kinase inhibitors; the authors note development of less toxic, highly selective FGFR3 inhibitors as rationale for trials in NMIBC PMID:28583311
Open questions
- FGFR3-TNIP2 was a single case finding in an n=105 cohort; functional confirmation of oncogenic activity and response to FGFR3 inhibitors has not been reported PMID:28583311
Sources
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