T Iwata1, T Tamanaha1, R Koezuka1, M Tochiya1, H Makino1, I Kishimoto1, N Mizusawa1, S Ono1, N Inoshita1, S Yamada1, A Shimatsu1, K Yoshimoto2. 1. 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. 2. 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.
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. DESIGN: 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. CONCLUSION: 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.
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. DESIGN: 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. CONCLUSION: 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: T Cuny; T T Mac; P Romanet; H Dufour; I Morange; F Albarel; A Lagarde; F Castinetti; T Graillon; M O North; A Barlier; T Brue Journal: Pituitary Date: 2019-10 Impact factor: 4.107
Authors: Crystal D C Kamilaris; Fabio R Faucz; Victoria C Andriessen; Naris Nilubol; Chyi-Chia Richard Lee; Mark A Ahlman; Fady Hannah-Shmouni; Constantine A Stratakis Journal: J Endocr Soc Date: 2021-01-25