title: Sequence analysis of the catalytic subunit of PKA in somatotroph adenomas.
abstract: OBJECTIVE
  The pathogenetic mechanisms of sporadic somatotroph adenomas are not well understood, but derangements of the cAMP pathway have been implicated. Recent studies have identified L206R mutations in the alpha catalytic subunit of protein kinase A (PRKACA) in cortisol-producing adrenocortical adenomas and amplification of the beta catalytic subunit of protein kinase A PRKACB in acromegaly associated with Carney complex. Given that both adrenocortical adenomas and somatotroph adenomas are known to be reliant on the cAMP signalling pathway, we sought to determine the relevance of the L206R mutation in both PRKACA and PRKACB for the pathogenesis of sporadic somatotroph adenomas.
  
  
  METHODS
  Somatotroph adenoma specimens, both frozen and formalin-fixed, from patients who underwent surgery for their acromegaly between 1995 and 2012, were used in the study.
  
  
  METHODS
  The DNA sequence at codon 206 of PRKACA and PRKACB was determined by PCR amplification and sequencing. The results were compared with patient characteristics, the mutational status of the GNAS complex locus and the tumour granulation pattern.
  
  
  RESULTS
  No mutations at codon 206 of PRKACA or PRKACB were found in a total of 92 specimens, comprising both WT and mutant GNAS cases, and densely, sparsely and mixed granulation patterns.
  
  
  CONCLUSIONS
  It is unlikely that mutation at this locus is involved in the pathogenesis of sporadic somatotroph adenoma; however, gene amplification or mutations at other loci or in other components of the cAMP signalling pathway, while unlikely, cannot be ruled out.
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK sarah.larkin@ndcn.ox.ac.uk.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Larkin
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
authors.forename: Niki
authors.initials: N
authors.lastname: Karavitaki
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Hernández-Ramírez
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
authors.forename: Olaf
authors.initials: O
authors.lastname: Ansorge
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.affiliation: Nuffield Department of Clinical NeurosciencesDepartment of Neuropathology, Level 1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UKDepartment of EndocrinologyBarts and London School of Medicine, Queen Mary University of London, London EC1A 6BQ, UKDepartment of EndocrinologyOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000235:genetics*; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D047368:Tumor Burden / Q000235:genetics; D055815:Young Adult
chemical_list: D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human