Premature thelarche and granulosa cell tumors: a search for FSH receptor and G5alpha activating mutations.
Activating mutations of the Gsalpha gene are responsible for McCune-Albright syndrome and have also been identified in sporadic tumors of the pituitary and thyroid. When associated with malignancy, activating Gsalpha mutations are known as gsp-oncogenes. We hypothesized that similar activating mutations might also account for some cases of premature thelarche and/ or granulosa cell tumors. Polymerase chain reaction and DNA sequencing was used to screen for activating mutations of Gsalpha genes in children with premature thelarche and in pathologic specimens from juvenile and adult granulosa cell tumors. Because these disorders involve over-activity of the FSH-signaling pathway, we also screened for activating mutations of the FSH receptor. No mutations were detected in either the Gsalpha or the FSHR fragment studied. Previously reported polymorphisms (Ser680Asn and Ala307Thr) of the FSHR were detected in 25/27 tumor samples and 9/9 premature thelarche samples. We conclude that activating mutations in previously identified mutation 'hot-spots' in the Gsalpha and FSH receptor genes are probably not a major cause of premature thelarche or granulosa cell tumors. In contrast, polymorphisms of the FSH receptor are common.
Hannon
Tamara S
TS
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis 46202, USA. tshannon@iupui.edu
King
Denise Walker
DW
Brinkman
Abigail D
AD
Steinmetz
Rosemary
R
Davis
Mary M
MM
Eugster
Erica A
EA
Pescovitz
Ora H
OH
D000365:Age Determination by Skeleton; D001120:Arginine / Q000235:genetics; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000502:physiology; D005820:Genetic Testing; D006106:Granulosa Cell Tumor / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011629:Puberty, Precocious / Q000235:genetics*; D011962:Receptors, FSH / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011962:Receptors, FSH; D004247:DNA; D001120:Arginine; D019205:GTP-Binding Protein alpha Subunits, Gs