Low prevalence of Gs alpha mutations in śomatotroph adenomas of children and adolescents.
Mutations in the gene coding for the alpha-subunit of the heterotrimeric stimulatory G protein Gs are the most frequently identified molecular events in the development of somatotroph adenomas in adults. In children and adolescents, somatotroph adenomas are rare, and only two cases with the Gs alpha mutation have been reported so far. In this study, we therefore investigated the prevalence of activating Gs alpha mutations in 17 patients younger than 20 years with pituitary growth hormone-secreting adenomas and examined the characteristics of mutation-positive cases. The most common C-->T substitution in codon 201 was detected in two children. Interestingly, in contrast to the remaining cases, the adenomas positive for the Gs alpha mutation proved to be nonsporadic, but part of a syndrome associated with endocrine tumors in both individuals. Additional tests confirmed McCune-Albright syndrome in the first patient and multiple endocrine neoplasia type 1 syndrome in the second patient. In contrast to the findings in adult cases, somatotroph adenomas in young patients seem to carry somatic Gs alpha mutations at a lower frequency, and germ-line or early postzygotic mutational events may be responsible for the shortened latency of tumorigenesis.
Metzler
Markus
M
Department of Pediatrics, University of Erlangen-Nuremberg, Loschgestr. 15, 91054 Erlangen, Germany.
Luedecke
Dieter K
DK
Saeger
Wolfgang
W
Grueters
Annette
A
Haberl
Hannes
H
Kiess
Wieland
W
Repp
Reinald
R
Rascher
Wolfgang
W
Doetsch
Joerg
J
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D015183:Restriction Mapping
D019205:GTP-Binding Protein alpha Subunits, Gs