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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.

journal_name

Clin Endocrinol (Oxf)

journal_title

Clinical endocrinology

authors

Yamasaki H,Mizusawa N,Nagahiro S,Yamada S,Sano T,Itakura M,Yoshimoto K

doi

10.1046/j.1365-2265.2003.01740.x

keywords:

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

464-70

issue

eissn

0300-0664

issn

1365-2265

pii

1740

journal_volume

pub_type

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