title: Polyclonal origin of medullary carcinoma of the thyroid in multiple endocrine neoplasia type 2.
abstract: Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC) and other tumors. Since MTC can also occur in a sporadic form and as familial medullary thyroid carcinoma, this neoplasm offers a unique opportunity to investigate the difference of origin, if any, between the sporadic and the hereditary forms of a tumor. While sporadic malignancies have usually been found to result from a mutational event occurring at the single-cell level and are therefore monoclonal, studies on hereditary neoplasms have been scarce and often produced conflicting results. In order to determine the clonal origin of sporadic MTCs and of those occurring in MEN 2 syndromes we used a clonality assay based on a polymorphic trinucleotide repeat of the X-linked human androgen-receptor gene. We found that 10 out of 11 MTCs expressed a polyclonal pattern of X inactivation, including a significant percentage of the cases clinically defined as sporadic.
authors.affiliation: Dipartimento di Oncologia Clinica e Sperimentale, University of Genoa, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Ferraris
authors.forename: R
authors.initials: R
authors.lastname: Mangerini
authors.forename: G F
authors.initials: GF
authors.lastname: Gaetani
authors.forename: C
authors.initials: C
authors.lastname: Romei
authors.forename: A
authors.initials: A
authors.lastname: Pinchera
authors.forename: F
authors.initials: F
authors.lastname: Pacini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000235:genetics / Q000473:pathology*; D002999:Clone Cells; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics / Q000473:pathology*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; C037130:GCGC-specific type II deoxyribonucleases