POLYCLONAL ORIGIN OF MEDULLARY CARCINOMA OF THE THYROID IN MULTIPLE ENDOCRINE NEOPLASIA TYPE-2

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 fami lial medullary thyroid carcinoma, this neoplasm offers a unique opport unity to investigate the difference of origin, if any, between the spo radic and the hereditary forms of a tumor, While sporadic malignancies have usually been found to result from a mutational event occurring a t the single-cell level and are therefore monoclonal, studies on hered itary neoplasms have been scarce and often produced conflicting result s. In order to determine the clonal origin of sporadic MTCs and of tho se occurring in MEN 2 syndromes we used a clonality assay based on a p olymorphic trinucleotide repeat of the X-linked human androgen-recepto r gene. We found that 10 out of 11 MTCs expressed a polyclonal pattern of X inactivation, including a significant percentage of the cases cl inically defined as sporadic.