Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters.

Abstract

Although somatic mutations have been identified in a subset of thyroid nodules, the pathogenesis of nodules in multinodular goiters remains unclear. Clonal analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell. Individual thyroid nodules have been shown to be of polyclonal or monoclonal origin. In this study we examined the clonality of several different nodules in patients with multinodular goiters. Clonality was established using the X-chromosomal probe M27 beta, which detects a multiallelic polymorphism at the locus DXS255 in 90% of females. Twenty-five nodules from 9 multinodular goiters were analyzed; 9 nodules were polyclonal, and 16 were monoclonal. Three goiters contained only polyclonal nodules, whereas 3 contained only monoclonal nodules. Polyclonal and monoclonal nodules coexisted in 3 goiters. In 2 goiters, the monoclonal nodules were shown to derive from different progenitor cells. We conclude that polyclonal and monoclonal nodules may coexist in multinodular goiters and that monoclonal nodules can originate from different cells. The coexistence of polyclonal and monoclonal nodules suggests that different pathogenic mechanisms occur simultaneously or that monoclonal nodules emerge secondarily from a polyclonal population due to a growth advantage from a genetically altered cell.

Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.

“…The clonal composition of this tumor was determined by X-inactivation analysis and found to be polyclonal, suggesting the presence of a hyperplastic lesion. This contrasts with the findings in this study and the demonstration that the majority of solitary nodules and nodules from multinodular goiters are of monoclonal origin (36,37).…”

Functional characterization of multiple DICER1 mutations in an adolescent

“…2B). It is notable that we observed the same two-hit phenomenon in the MNG (Supplementary Figure 7), as goiter can be either monoclonal or polyclonal in nature (Kopp et al 1994). Moreover, MNG is not classified by the World Health Organization as a neoplasm, but as a benign hyperplasia (Horowitz et al 2004).…”

Congenital Hyperthyroidism Caused by a Mutation in the Thyrotropin-Receptor Gene

“…29 In addition, the patient had thyroid nodules that were p resumably caused by additional mutations in other genes. 30 Although congenital nonautoimmune hyperthyroidism is rare, it is important to distinguish this disorder from the more common congenital autoimmune hyperthyroidism, because nonautoimmune hyperthyroidism can be severe and does not remit. Furthermore, because of its presumably early onset during fetal development, the disorder could have irreversible consequences if untreated.…”