title: Germline deletion and a somatic mutation of the PRKAR1A gene in a Carney complex-related pituitary adenoma.
abstract: OBJECTIVE
  The objective was to assess involvement of loss of the PRKAR1A gene encoding a type 1α regulatory subunit of cAMP-dependent protein kinase A located on 17q24 in a Carney complex (CNC)-related pituitary adenoma.
  
  
  METHODS
  We investigated aberrations of the PRKAR1A gene in a CNC patient with a GH-producing pituitary adenoma, whose family has three other members with probable CNC.
  
  
  METHODS
  A gene mutation was identified by a standard DNA sequencing method based on PCR. DNA copy number was measured to evaluate allelic loss on 17q24 by quantitative PCR. The breakpoints of deletion were determined by cloning a rearranged region in the deleted allele.
  
  
  RESULTS
  A PRKAR1A mutation of c.751_758del8 (p.S251LfsX16) was found in genomic DNA obtained from a pituitary adenoma, but not leukocytes from the patient. Reduced DNA copy number at loci including the PRKAR1A gene on 17q24 was detected in both the tumor and leukocytes, suggesting a deletion at the loci at the germline level. The deletion size was determined to be ∼ 0.5 Mb and this large deletion was also found in two other family members.
  
  
  CONCLUSIONS
  This is the first case showing a CNC-related pituitary adenoma with the combination of somatic mutation and a large inherited deletion of the PRKAR1A gene. Biallelic inactivation of PRKAR1A appears to be necessary for the development of CNC-related pituitary adenoma.
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tamanaha
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Koezuka
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tochiya
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Makino
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Kishimoto
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mizusawa
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Inoshita
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Shimatsu
authors.affiliation: Department of Medical PharmacologyInstitute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, JapanDepartment of Endocrinology and MetabolismNational Cerebral and Cardiovascular Center, Osaka, JapanDepartments of PathologyHypothalamic and Pituitary SurgeryToranomon Hospital, Tokyo, JapanClinical Research InstituteNational Hospital Organization Kyoto Medical Center, Kyoto, Japan yoshimoto@tokushima-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D056733:Carney Complex / Q000175:diagnosis / Q000235:genetics*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human