Background: Familial nonmedullary thyroid carcinoma (FNMTC) is a clinical entity characterized by a more aggressive phenotype than the sporadic counterpart. The transmission of susceptibility of FNMTC is compatible with autosomal dominant inheritance. We report the identification of a new entity of FNMTC and the mapping of the responsible gene named TCO (for thyroid tumor with cell oxyphilia).
Methods: In one family, multinodular goiters were diagnosed in six individuals and papillary thyroid carcinoma was diagnosed in three. Eight patients were operated on. Blood samples were collected from the nine affected patients and from eight unaffected relatives. The gene was mapped by linkage analysis with a whole-genome panel of microsatellite markers.
Results: The neoplastic cells from all lesions showed characteristic faint to marked cytoplasmic oxyphilia. We found a logarithm of odd ratio (LOD) score of 2.41 at theta = 0 for marker D19S586. Additional markers were typed in the region and were found to be in linkage, with LOD scores peaking at markers D19S916 (Zmax = 3.01 at theta = 0) and D19S413 (Zmax = 2.95 at theta = 0). All these markers have been physically mapped to 19p13.2.
Conclusions: TCO was mapped to chromosome 19p13.2. Interestingly, both the benign and malignant thyroid tumors in this family exhibit some degree of oxyphilia, which has not been described until now in the familial forms of NMTC.