PRKACA

Overview

PRKACA encodes the catalytic alpha subunit of cAMP-dependent protein kinase A (PKA). PKA is a central effector of cAMP signaling and plays a role in adrenal gland biology and tumorigenesis. PRKACA is grouped within the kinase signaling axis of pheochromocytoma/paraganglioma (PCC/PGL) molecular classification, alongside RET, NF1, HRAS, and PRKAR1A.

Alterations observed in the corpus

  • Grouped within the cAMP-dependent PKA kinase signaling axis in PCC/PGL molecular pathway analysis, alongside PRKAR1A and other kinase-signaling drivers (RET, NF1, HRAS, BRAF, FGFR, NGFR); relevant to the kinase signaling mRNA subtype in a TCGA multi-platform study of 173 PCC/PGL tumors PMID:28162975
  • DNAJB1-PRKACA fusion identified as pathognomonic for fibrolamellar hepatocellular carcinoma (FLC) in 10,336 MSK-IMPACT cases PMID:28481359
  • The DNAJB1–PRKACA fusion is liver-specific, recovered exclusively in fibrolamellar carcinoma (FLC subtype of LIHC) across 9,624 TCGA pan-cancer samples, corroborating Dinh et al. 2017 PMID:29617662.

Cancer types (linked)

  • Pheochromocytoma (PHC) and paraganglioma (PGNG): PRKACA is part of the kinase signaling pathway axis associated with the kinase signaling molecular subtype in the TCGA PCPG cohort PMID:28162975

Co-occurrence and mutual exclusivity

  • Co-grouped with PRKAR1A in the cAMP/PKA signaling sub-axis of kinase signaling PCC/PGL; driver mutations in this group are mutually exclusive with pseudohypoxia, Wnt, and Krebs-cycle driver mutations (p < 1e-4) PMID:28162975

Therapeutic relevance

  • No direct therapeutic targeting of PRKACA reported in this corpus; kinase-signaling-subtype PCC/PGLs (defined by RET, NF1, HRAS mutations) are associated with better aggressive-disease-free survival vs other subtypes PMID:28162975

Open questions

  • The specific contribution of PRKACA alterations (as distinct from PRKAR1A) to PCC/PGL tumorigenesis in the TCGA cohort requires further delineation; no recurrent PRKACA somatic mutations were identified as MutSig2 significant in this dataset PMID:28162975

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:29617662

This page was processed by wiki-cli on 2026-05-15.