PRDM6
Overview
PRDM6 encodes a SET-domain-containing transcriptional repressor. In Group 4 medulloblastoma it is the most prevalent driver, activated by SNCAIP-locus tandem duplications that reposition a Group 4-specific super-enhancer into the PRDM6-containing TAD via enhancer hijacking.
Alterations observed in the corpus
- SET-domain protein activated by SNCAIP-locus tandem duplications in 17% of Group 4 medulloblastoma (most prevalent Group 4 driver); PRDM6 expression is upregulated ≥20-fold in SV-positive vs. SV-negative cases (P=6.07×10⁻²⁴); SV breakpoints cluster near CTCF sites at the TAD boundary separating SNCAIP and PRDM6, repositioning a Group 4-specific super-enhancer into the PRDM6-containing TAD PMID:28726821
Cancer types (linked)
- MB: most prevalent Group 4 driver; restricted to Group 4 medulloblastoma in a 491-sample WGS/WES pan-MB cohort; nominated as a new actionable target pending functional validation PMID:28726821
Co-occurrence and mutual exclusivity
- Activates in the same Group 4 context as SNCAIP tandem duplications (mechanistically upstream); mutually exclusive with other Group 4 enhancer-hijacking events targeting GFI1/GFI1B PMID:28726821
Therapeutic relevance
- Nominated as a new actionable target in Group 4 medulloblastoma, but functional validation of PRDM6 methyltransferase activity and its essentiality is pending before clinical translation PMID:28726821
Open questions
- The oncogenic mechanism (altered substrate recognition vs. gain of methyltransferase activity) and whether PRDM6 is directly druggable remain to be established experimentally.
Sources
This page was processed by crosslinker on 2026-05-15.