Mutation analysis of protein kinase A catalytic subunit in thyroid adenomas and pituitary tumours

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.