PRKCD
Overview
PRKCD (Protein Kinase C Delta) encodes a serine/threonine kinase involved in apoptosis and B-cell signaling. Biallelic inactivation of PRKCD is a novel PCNSL-specific finding, not recurrently altered in systemic DLBCL, suggesting a unique role in CNS lymphoma pathogenesis.
Alterations observed in the corpus
- In primary central nervous system lymphoma (PCNSL), PRKCD undergoes biallelic inactivation: splice-donor mutations (plus p.W608S missense in one case) co-occurring with monoallelic deletion of PRKCD in 2/10 WES cases; focal monoallelic deletions (<1 Mb) in an additional 3/18 aCGH cases. This pattern of biallelic inactivation is not reported in nodal DLBCL (COSMIC lists only 1/1,058 hematologic samples with PRKCD alteration). PMID:25991819
Cancer types (linked)
- PCNSL: PCNSL-specific biallelic inactivation via splice-donor mutation + monoallelic deletion; not seen in systemic DLBCL. PMID:25991819
Co-occurrence and mutual exclusivity
- Losses of 3p21.31 (PRKCD) and 6q23 (TNFAIP3) were rare in 12q-gained PCNSL cases, suggesting mutual exclusivity with the 12q gain pattern. PMID:25991819
Therapeutic relevance
- Loss of PRKCD expression has been linked to radiation resistance in cervical cancer (via MiR-181a); the authors speculate this could extrapolate to PCNSL, suggesting PRKCD status as a candidate biomarker for radiation responsiveness. PMID:25991819
Open questions
- No functional validation of PRKCD loss in PCNSL models — pathogenic role is inferred from recurrence and prior B/T-cell biology literature. PMID:25991819
Sources
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