Mapping of a gene predisposing to familial thyroid tumors with cell oxyphilia to chromosome 19 and exclusion of JUN B as a candidate gene

Background, Familial nonmedullary thyroid carcinoma (FNMTC) is a clinical e ntity characterized by a move aggressive phenotype than the sporadic counte rpart. The transmission of susceptibility of FNMTC is compatible with autos omal 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 individu als and papillary thyroid carcinoma teas diagnosed in three. Eight patients were operated on. Blood samples were collected from the nine affected pati ents and from eight unaffected relatives. The gene was mapped by linkage an alysis 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) sc ore 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 m arkers D19S916 (Z(max) = 3.01 at theta = 0) and D19S413 (Z(max) = 2.95 at t heta = 0). All these markers have been physically mapped to 19p13.2. Conclusions. TCO was mapped to chromosome 19p13.2. Interestingly both the b enign and malignant thyroid tumors in this family exhibit some degree of ox yphilia, which has not been described until now in the familial forms of NM TC.