PRKAR1A

Overview

PRKAR1A encodes the regulatory subunit 1A of cAMP-dependent protein kinase A (PKA), which normally inhibits PKA catalytic activity. Loss-of-function mutations in PRKAR1A cause Carney complex, a multiple neoplasia syndrome with predisposition to adrenocortical tumors, myxomas, and schwannomas. In pheochromocytoma/paraganglioma (PCC/PGL), PRKAR1A is grouped within the kinase signaling axis alongside PRKACA and other kinase drivers.

Alterations observed in the corpus

  • Grouped within the cAMP-dependent PKA kinase signaling axis in PCC/PGL molecular pathway analysis alongside PRKACA 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

Cancer types (linked)

  • Pheochromocytoma (PHC) and paraganglioma (PGNG): PRKAR1A 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 PRKACA 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 PRKAR1A reported in this corpus; kinase-signaling-subtype PCC/PGLs are associated with better aggressive-disease-free survival vs other subtypes PMID:28162975

Open questions

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

Sources

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