GH-secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23-24.

Abstract

OBJECTIVE:

The molecular events leading to the development of GH-secreting pituitary tumours remain largely unknown. Gsalpha (GNAS1) mutations are found in 27-43% of sporadic GH-secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4-9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH-secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RIalpha regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) on 17q23-24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH-secreting adenomas in about 10%. We re-evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH-secreting adenomas.

DESIGN:

We analysed exons 8 and 9 of GNAS1 and all exons and the exon-intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH-secreting pituitary adenomas (30 GH-secreting adenomas, two GH and PRL-secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23-24 with four microsatellite markers and intragenic markers of PRKAR1A.

RESULTS:

Seventeen of 32 (53.1%) tumours showed somatic-activating mutations of GNAS1: 16 (53.3%) of 30 GH-secreting adenomas and one of two GH and PRL-secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23-24 were detected in any of the tumours examined.

CONCLUSION:

We reconfirm the important role of activating mutations of GNAS1 in GH-secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis.

• Authors: Hiroyuki Yamasaki, Noriko Mizusawa, Shinji Nagahiro, Shozo Yamada, Toshiaki Sano, Mitsuo Itakura, Katsuhiko Yoshimoto
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 58 Issue 4 Pg. 464-70 (Apr 2003) ISSN: 0300-0664 [Print] England
• PMID: 12641630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
• PRKAR1A protein, human
• Growth Hormone
• Growth Hormone-Releasing Hormone
• Cyclic AMP-Dependent Protein Kinases

Topics

• Adenoma (diagnosis, genetics, metabolism)
• Adult
• Aged
• Chromosomes, Human, Pair 17
• Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
• Cyclic AMP-Dependent Protein Kinases (genetics)
• Female
• Gene Silencing
• Growth Hormone (blood, metabolism)
• Growth Hormone-Releasing Hormone
• Humans
• Loss of Heterozygosity
• Male
• Middle Aged
• Pituitary Neoplasms (diagnosis, genetics, metabolism)
• Polymerase Chain Reaction
• Statistics, Nonparametric