CSNK2B
Overview
CSNK2B encodes the regulatory beta subunit of Casein Kinase 2 (CK2), a constitutively active serine/threonine kinase with roles in WNT pathway regulation, cell survival, and the DNA damage response. CK2 phosphorylates components of the beta-catenin destruction complex and has been implicated in modulating WNT/beta-catenin signaling activity. In medulloblastoma, CSNK2B emerges as a recurrently mutated gene specifically enriched in the WNT subgroup, suggesting a cooperative role with CTNNB1 mutations in driving aberrant WNT pathway activation.
Alterations observed in the corpus
- CSNK2B is recurrently mutated in medulloblastoma WES of 92 tumors (Broad cohort), with mutations co-occurring with CTNNB1 mutations in the WNT subgroup, implicating it as a cooperative driver in WNT-subgroup medulloblastoma PMID:22820256
- Clinically actionable mutation identified in 14% of WNT-subgroup medulloblastomas in the ICGC/CBTTC cohort (n=491) PMID:28726821.
Cancer types (linked)
- MB (medulloblastoma): Recurrent mutations in the WNT subgroup, co-occurring with CTNNB1 activating mutations; Broad WES cohort (92 tumors) PMID:22820256
Co-occurrence and mutual exclusivity
- CSNK2B mutations co-occur with CTNNB1 mutations in the WNT subgroup of medulloblastoma PMID:22820256
Therapeutic relevance
- CK2 inhibitors are under investigation in other cancer contexts; the co-occurrence of CSNK2B and CTNNB1 mutations in WNT-subgroup medulloblastoma may define a subset with therapeutic vulnerability to combined WNT pathway targeting PMID:22820256
Open questions
- Whether CSNK2B mutations are driver events or passengers in the context of CTNNB1-mutant WNT medulloblastoma is not established.
Sources
- PMID:22820256 — Medulloblastoma WES (Broad, 92 tumors)
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