Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21

The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex gen etic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most comm on form of NMTC, an extensive genomewide scan revealed a common haplotype o n chromosome 2q21 in seven of the eight patients with PTC. To verify the si gnificance of the 2q21 locus, we performed linkage analysis in an independe nt sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD scor e (HLOD) of 3.07 (alpha = 0.42), nonparametric linkage (NPL) 3.19, () at ma rker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, i dentified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha = 0.80) and NPL = 4.99 (P = .00002) at markers AFMa272zg9 and D2S2271, respe ctively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.