Protein kinase A defects and cortisol-producing adrenal tumors

Current Opinion in Endocrinology, Diabetes and Obesity

Volumn 22, Issue 3, 2015, Pages 157-162

  Zilbermint, Mihail ^a   Stratakis, Constantine A ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

adrenal tumor; cortisol producing adrenal adenoma; Cushing syndrome; protein kinase A; protein kinase catalytic subunit alpha; protein kinase catalytic subunit beta; protein kinase type 1 alpha regulatory subunit

Indexed keywords

CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; HYDROCORTISONE; CYCLIC AMP DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT; PRKACA PROTEIN, HUMAN;

ADRENAL HYPERPLASIA; ADRENAL TUMOR; CARNEY COMPLEX; CUSHING SYNDROME; GENE AMPLIFICATION; HUMAN; POINT MUTATION; PROTEIN DEFECT; PROTEIN KINASE A DEFECT; REVIEW; SIGNAL TRANSDUCTION; TUMOR VOLUME; ADRENAL CORTEX ADENOMA; GENETICS;

ADRENAL GLAND NEOPLASMS; ADRENOCORTICAL ADENOMA; CUSHING SYNDROME; CYCLIC AMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNITS; HUMANS;

EID: 84928542954     PISSN: 1752296X     EISSN: 17522978     Source Type: Journal    
DOI: 10.1097/MED.0000000000000149     Document Type: Review

References (48)

1. Young WF. The incidentally discovered adrenal mass. N Engl J Med 2007; 356:601-610.
2. Stratakis CA. Cushing syndrome caused by adrenocortical tumors and hyperplasias (corticotropin-independent Cushing syndrome). Endocr Dev 2008; 13:117-132.
3. Kirschner LS, Sandrini F, Monbo J, et al. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Hum Mol Genet 2000; 9:3037-3046.
4. Elbelt U, Trovato A, Kloth M, et al. Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma. J Clin Endocrinol Metab 2015; 100:E119-E128.
5. Gagliardi L, Schreiber AW, Hahn CN, et al. ARMC5 mutations are common in familial bilateral macronodular adrenal hyperplasia. J Clin Endocrinol Metab 2014; 99:E1784-1792.
6. Alencar GA, Lerario AM, Nishi MY, et al. ARMC5 mutations are a frequent cause of primary macronodular adrenal Hyperplasia. J Clin Endocrinol Metab 2014; 99:E1501-E1509.
7. Faucz FR, Zilbermint M, Lodish MB, et al. Macronodular adrenal hyperplasia due to mutations in an armadillo repeat containing 5 (ARMC5) gene: A clinical and genetic investigation. J Clin Endocrinol Metab 2014; 99: E1113-E1119.
8. Assie G, Libe R, Espiard S, et al. ARMC5 mutations in macronodular adrenal hyperplasia with Cushing's syndrome. N Engl J Med 2013; 369:2105-2114.
9. Boikos SA, Horvath A, Heyerdahl S, et al. Phosphodiesterase 11A expression in the adrenal cortex, primary pigmented nodular adrenocortical disease, and other corticotropin-independent lesions. Horm Metab Res 2008; 40:347-353.
10. Horvath A, Boikos S, Giatzakis C, et al. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 2006; 38:794-800.
11. Horvath A, Mericq V, Stratakis CA. Mutation in PDE8B, a cyclic AMP-specific phosphodiesterase in adrenal hyperplasia. N Engl J Med 2008; 358:750-752.
12. Libe R, Fratticci A, Coste J, et al. Phosphodiesterase 11A (PDE11A) and genetic predisposition to adrenocortical tumors. Clin Cancer Res 2008; 14:4016-4024.
13. de Joussineau C, Sahut-Barnola I, Levy I, et al. The cAMP pathway and the control of adrenocortical development and growth. Mol Cell Endocrinol 2012; 351:28-36.
14. Scott JD. Cyclic nucleotide-dependent protein kinases. Pharmacol Ther 1991; 50:123-145.
15. Das R, Esposito V, Abu-Abed M, et al. cAMP activation of PKA defines an ancient signaling mechanism. Proc Natl Acad Sci U S A 2007; 104:93-98.
16. Meoli E, Bossis I, Cazabat L, et al. Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors. Cancer Res 2008; 68:3133-3141.
17. Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985; 64:270-283.
18. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 2001; 86:4041-4046.
19. Rothenbuhler A, Stratakis CA. Clinical and molecular genetics of Carney complex. Best practice & research. Clin Endocrinol Metab 2010; 24:389-399.
20. Stratakis CA, Sarlis N, Kirschner LS, et al. Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999; 131:585-591.
21. Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000; 26:89-92.
22. Stratakis CA, Carney JA, Lin JP, et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996; 97:699-705.
23. Horvath A, Bossis I, Giatzakis C, et al. Large deletions of the PRKAR1A gene in Carney complex. Clin Cancer Res 2008; 14:388-395.
24. Anselmo J, Medeiros S, Carneiro V, et al. A large family with Carney complex caused by the S147G PRKAR1A mutation shows a unique spectrum of disease including adrenocortical cancer. J Clin Endocrinol Metab 2011; 97:351-359.
25. Morin E, Mete O, Wasserman JD, et al. Carney complex with adrenal cortical carcinoma. J Clin Endocrinol Metab 2012; 97:E202-206.
26. Gennari M, Stratakis CA, Hovarth A, et al. A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations. Clin Endocrinol (Oxf) 2008; 69:751-755.
27. Gaujoux S, Tissier F, Ragazzon B, et al. Pancreatic ductal and acinar cell neoplasms in Carney complex: A possible new association. J Clin Endocrinol Metab 2011; 96:E1888-E1895.
28. Beuschlein F, Fassnacht M, Assie G, et al. Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. N Engl J Med 2014; 370:1019-1028.
29. Cao Y, He M, Gao Z, et al. Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. Science 2014; 344:913-917.
30. Di Dalmazi G, Kisker C, Calebiro D, et al. Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: A European multicentric study. J Clin Endocrinol Metab 2014; 99:E2093-E2100.
31. Goh G, Scholl UI, Healy JM, et al. Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. Nat Genet 2014; 46:613-617.
32. Sato Y, Maekawa S, Ishii R, et al. Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. Science 2014; 344:917-920.
33. Nakajima Y, Okamura T, Gohko T, et al. Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with several adrenal adenomas secreting cortisol [Rapid Communication]. Endocr J 2014; 61:825-832.
34. Carney JA, Lyssikatos C, Lodish MB, Stratakis CA. Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes. Hum Pathol 2015; 46:40-49.
35. Calebiro D, Hannawacker A, Lyga S, et al. PKA catalytic subunit mutations in adrenocortical Cushing's adenoma impair association with the regulatory subunit. Nat Commun 2014; 5:5680.
36. Giordano TJ. Genetics: pinpointing a hotspot in adrenal Cushing syndrome. Nat Rev Endocrinol 2014; 10:447-448.
37. Forlino A, Vetro A, Garavelli L, et al. PRKACB and Carney complex. N Engl J Med 2014; 370:1065-1067.
38. Espiard S, Ragazzon B, Bertherat J. Protein kinase a alterations in adrenocortical tumors. Horm Metab Res 2014; 46:869-875.
39. Kirschner LS. Medicine. A unified cause for adrenal Cushing's syndrome. Science 2014; 344:804-805.
40. Sargent J. Neuroendocrine cancer. An activating hotspot mutation in PRKACA provides clues for adrenal Cushing syndrome therapeutics. Nat Rev Endocrinol 2014; 10:311.
41. Stratakis CA. E pluribus unum? The main protein kinase A catalytic subunit (PRKACA), a likely oncogene, and cortisol-producing tumors. J Clin Endocrinol Metab 2014; 99:3629-3633.
42. Cancer: PKA mutations are associated with Cushing syndrome. Nat Rev Endocrinol 2014; 10:251-1251.
43. Stratakis CA, Bertherat J. PDE 2013, Paris, France: Another exciting workshop for cyclic AMP, protein kinase A, and phosphodiesterases. Horm Metab Res 2014; 46:825-826.
44. Bertagna X. Genetics of adrenal diseases in 2014: Genetics improves understanding of adrenocortical tumours. Endocrinology 2015; 11:77-78.
45. Moody SE, Schinzel AC, Singh S, et al. PRKACA mediates resistance to HER2-targeted therapy in breast cancer cells and restores antiapoptotic signaling. Oncogene 2014. (in press).
46. Honeyman JN, Simon EP, Robine N, et al. Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science 2014; 343:1010-1014.
47. Walkley CR, Walia MK, Ho PW, Martin TJ. PTHrP, its receptor, and protein kinase A activation in osteosarcoma. Mol Cell Oncol 2014. (in press).
48. Vitali E, Peverelli E, Giardino E, et al. Cyclic adenosine 30-50-monophosphate (cAMP) exerts proliferative and antiproliferative effects in pituitary cells of different types by activating both cAMP-dependent protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac). Mol Cell Endocrinol 2014; 383:193-202.