UBTF
Overview
UBTF (Upstream Binding Transcription Factor) encodes a component of the RNA polymerase I transcription machinery. In pheochromocytoma and paraganglioma (PCC/PGL), UBTF was identified as a 5′ fusion partner in recurrent UBTF–MAML3 in-frame fusion genes that drive MAML3 overexpression and define the Wnt-altered molecular subtype.
Alterations observed in the corpus
- Acts as the 5′ fusion partner in UBTF–MAML3 fusion genes in PCC/PGL; its promoter drives MAML3 overexpression (2.7-fold, p < 5e-6), defining the Wnt-altered subtype and serving as a clinical marker of metastasis and poor aggressive-disease-free survival PMID:28162975
- UBTF–MAML3 fusions occurred in 7 of 10 MAML3 fusion-positive tumors, associated with co-amplification of chromosomes 4q31.1 and 17q21.31 (p < 2e-9) PMID:28162975
Cancer types (linked)
- PHC / PGNG: UBTF–MAML3 fusions were specific to the Wnt-altered molecular subtype of PCC/PGL (sporadic adrenal PCCs); all MAML3 fusion-positive tumors fell within this subtype (p < 4e-9) PMID:28162975
Co-occurrence and mutual exclusivity
- UBTF–MAML3 fusions occur in tumors without germline susceptibility-gene mutations; mutually exclusive with kinase signaling and pseudohypoxia driver events PMID:28162975
- The authors note that UBTF (the upstream fusion partner) may contribute tumorigenic properties beyond simply driving MAML3 overexpression, but this is unresolved PMID:28162975
Therapeutic relevance
- UBTF–MAML3 fusion-positive tumors activate Wnt/Hedgehog signaling; β-catenin antagonists (e.g., PRI-274) and STAT3 inhibitors (e.g., BB1608) are proposed as therapeutic hypotheses PMID:28162975
Open questions
- Whether UBTF itself contributes tumorigenic properties beyond driving MAML3 overexpression remains unresolved; direct ChIP-seq evidence for aberrant MAML3 genomic binding is lacking PMID:28162975
Sources
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