title: Parental origin of Gsalpha mutations in the McCune-Albright syndrome and in isolated endocrine tumors.
abstract: Activating mutations of the Gsalpha gene are detected in different endocrine tumors, such as GH-secreting adenomas and toxic thyroid adenomas, and in hyperfunctioning glands from patients with McCune-Albright syndrome (MAS). There is increasing evidence that the Gsalpha gene is subjected to imprinting control and that Gsalpha imprinting plays a key role in the pathogenesis of different human diseases. The aim of this study was to investigate the presence of a parent specificity of Gsalpha mutations in 10 patients affected with MAS and 12 isolated tumors (10 GH-secreting adenomas, one toxic thyroid adenoma, and one hyperfunctioning adrenal adenoma). The parental origin of Gsalpha mutations was assessed by evaluating NESP55 and exon 1A transcripts, which are monoallelically expressed from the maternal and paternal alleles, respectively. By this approach, we demonstrated that in isolated GH-secreting adenomas, as well as in MAS patients with acromegaly, Gsalpha mutations were on the maternal allele. By contrast, the involvement of other endocrine organs in MAS patients was not associated with a particular parent specificity, as precocious puberty and hyperthyroidism were present in patients with mutations on either the maternal or the paternal allele. Moreover, isolated hyperfunctioning thyroid and adrenal adenomas displayed the mutation on the maternal and paternal alleles, respectively. These data confirm the importance of Gsalpha imprinting in the pituitary gland and point out the high degree of tissue specificity of this phenomenon.
authors.affiliation: Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, 20122 Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantovani
authors.forename: Sara
authors.initials: S
authors.lastname: Bondioni
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Lania
authors.forename: Sabrina
authors.initials: S
authors.lastname: Corbetta
authors.forename: Luisa
authors.initials: L
authors.lastname: de Sanctis
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
authors.forename: Eliana
authors.initials: E
authors.lastname: Di Battista
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D002648:Child; D005220:Fathers; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D020125:Mutation, Missense; D010911:Pituitary Neoplasms / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D019205:GTP-Binding Protein alpha Subunits, Gs