TRRAP
Overview
TRRAP (Transformation/Transcription domain-Associated Protein) is a non-catalytic scaffold component of multiple histone acetyltransferase (HAT) complexes including SAGA and NuA4/TIP60. TRRAP is recruited to WNT-responsive gene targets by CTNNB1 (beta-catenin), linking WNT pathway activation to chromatin acetylation and transcriptional activation. In medulloblastoma, missense mutations in TRRAP occur specifically in the WNT molecular subgroup, identifying it as a chromatin-regulatory effector of oncogenic WNT signaling.
Alterations observed in the corpus
- Missense mutations in TRRAP identified in the WNT subgroup of medulloblastoma WGS (PCGP cohort, 37 tumors); TRRAP is recruited to WNT-responsive gene targets by CTNNB1 as part of a histone acetyltransferase complex PMID:22722829
- TRRAP identified as a newly mutated gene in TCC bladder cancer PMID:24121792
- TRRAP mutation present in the untreated TURBT primary (WCM117 rapid-autopsy case) but absent from post-chemotherapy metastases, indicating elimination of the TRRAP-mutant clone under platinum-based chemotherapy selection pressure. PMID:27749842
Cancer types (linked)
- Medulloblastoma (MBL): TRRAP missense mutations found in WNT subgroup; co-mutated with CTNNB1, SMARCA4, and MED13 alterations in WNT-driven tumors PMID:22722829
Co-occurrence and mutual exclusivity
- Co-occurs with CTNNB1 stabilizing mutations in the WNT subgroup of medulloblastoma; CTNNB1 recruits TRRAP to WNT-responsive promoters PMID:22722829
- Co-mutated with SMARCA4 (another chromatin remodeler) in WNT medulloblastoma PMID:22722829
Therapeutic relevance
- No direct targeted therapies identified for TRRAP-mutant tumors in the corpus. WNT subgroup medulloblastoma has favorable prognosis; TRRAP mutations may modulate WNT transcriptional output rather than acting as primary drivers.
Open questions
- Whether TRRAP mutations are gain-of-function (enhancing CTNNB1-driven transcription) or loss-of-function in WNT medulloblastoma is not established in the corpus.
Sources
- PMID:22722829 — Medulloblastoma WGS, 37 tumors, PCGP cohort
This page was processed by entity-page-writer on 2026-05-15. - PMID:24121792
This page was processed by entity-page-writer on 2026-05-15. - PMID:27749842
This page was processed by entity-page-writer on 2026-05-15.