RBPMS

Overview

RBPMS (RNA Binding Protein, mRNA Processing Factor) is an RNA-binding protein involved in mRNA processing and stability. In thyroid cancer genomics, RBPMS was identified as a novel 5’ fusion partner for NTRK3 in papillary thyroid carcinoma (PTC) by the TCGA comprehensive genomic analysis, highlighting its role as a fusion-driver gene in thyroid tumorigenesis.

Alterations observed in the corpus

  • RBPMS/NTRK3 fusion identified among the ETV6/NTRK3 and RBPMS/NTRK3 fusions detected in 6/484 (1.2%) combined papillary thyroid carcinomas (PTCs); these fusions exhibited a BRS-neutral (neither BRAFV600E-like nor RAS-like) expression phenotype and were mutually exclusive with BRAF/RAS/EIF1AX point mutations (Fisher’s exact p=4.9×10⁻⁴³ for all fusions vs. point mutations). PMID:25417114

Cancer types (linked)

  • THPA (Papillary Thyroid Carcinoma): RBPMS/NTRK3 fusion is a rare (frequency within the combined 1.2% NTRK fusion group) PTC driver alteration; BRS-neutral phenotype distinguishes it from BRAF- and RAS-driven PTCs. PMID:25417114

Co-occurrence and mutual exclusivity

  • RBPMS/NTRK3 fusions are mutually exclusive with BRAFV600E, RAS mutations, EIF1AX mutations, and other gene fusions (RET, BRAF, PAX8/PPARG, ALK, THADA) in PTC. PMID:25417114

Therapeutic relevance

  • NTRK3 fusions (including RBPMS/NTRK3) are potentially targetable with NTRK inhibitors (entrectinib, larotrectinib), which have demonstrated activity against TRK fusion-positive cancers including thyroid carcinomas. Specific RBPMS/NTRK3 data in thyroid cancer are limited to identification in this study. PMID:25417114

Open questions

  • The specific contribution of RBPMS versus ETV6 as NTRK3 fusion partners to clinical outcome or inhibitor sensitivity in PTC is not characterized.
  • Whether RBPMS/NTRK3 occurs in other thyroid cancer subtypes requires further study.

Sources

  • PMID:25417114 — TCGA integrated genomic characterization of 496 papillary thyroid carcinomas.

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