Ct. Esapa et Pe. Harris, Mutation analysis of protein kinase A catalytic subunit in thyroid adenomas and pituitary tumours, EUR J ENDOC, 141(4), 1999, pp. 409-412
Objective: The adenylyl cyclase system plays an important role in the contr
ol of both thyroid follicular and anterior pituitary cell function. Activat
ing mutations affecting important pathway components such as the TSH recept
or and Gs alpha occur in the majority of autonomously functioning thyroid n
odules, Only a small proportion of other types of thyroid tumours, however,
have been reported to harbour these mutations. Activating mutations of Gs
alpha have been reported to occur in up to 40% of pituitary somatotroph ade
nomas. As the majority of cold thyroid nodules and pituitary rumours are un
affected by these mutations, we have investigated the possibility of activa
ting mutations occurring in protein kinase A (PI(A), which is another key c
omponent of the adenylyl cyclase pathway.
Design: Genomic DNA and cDNA were analysed for the presence of PKA Ca mutat
ions by allele-specific oligonucleotide hybridisation and single strand con
formation polymorphism analysis.
Patients: A total of 171 tissue samples were investigated. These comprised
66 benign and 24 malignant thyroid neoplasms, 21 somatotroph adenomas, 35 n
on-functioning pituitary adenomas, 2 corticotroph adenomas, 1 malignant pro
lactinoma, and 22 normal pituitary tissue samples.
Results: No mutations of PKA C alpha were identified using either allele-sp
ecific olgonucleotide hybridisation or single strand conformation polymorph
ism analysis.
Conclusions: It appears that PKA C alpha mutations at the codons investigat
ed do not represent an oncogenetic mechanism in the development of thyroid
and pituitary neoplasms.