Thyroid Cancer, Nonmedullary, 3

Description

Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. The remaining cancers originate from parafollicular cells (medullary thyroid cancer, MTC; 155240). NMTC is classified into 4 groups: papillary, follicular, Hurthle cell (607464), and anaplastic. Approximately 5% of NMTC is hereditary, occurring as a minor component of a familial cancer syndrome (e.g., familial adenomatous polyposis 175100, Carney complex 160980) or as a primary feature (familial NMTC or FNMTC). Papillary thyroid cancer (PTC) is the most common histologic subtype of FNMTC, accounting for approximately 85% of cases (summary by Vriens et al., 2009).

For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550).

Mapping

McKay et al. (2001) studied a large Tasmanian pedigree with papillary thyroid carcinoma (PTC), the most common form of NMTC, that had been reported by Burgess et al. (1997) and McKay et al. (1999). In linkage studies they used the same microsatellite markers that had been used in previous studies to map a variant of familial papillary thyroid cancer associated with cell oxyphilia (TCO; 603386) and with familial multinodular goiter (MNG1; 138800) to 19p and 14q, respectively. The lod scores in the larger Tasmanian family excluded both of these loci. In addition, the candidate genes RET (164761), TRK (191315), MET (164860), TSHR (603372), APC (611731), and PTEN (601728) were excluded using microsatellite markers positioned in or in close proximity to these genes. An extensive genomewide scan in this family revealed a common haplotype on 2q21 in 7 of the 8 patients with PTC. To verify the significance of the 2q21 locus, the authors performed linkage analysis in an independent sample of 80 pedigrees, which yielded a multipoint heterogeneity lod score (hlod) of 3.07 and a nonparametric linkage (NPL) of 3.19 at marker D2S2271. Stratification based on the presence of at least 1 case of the follicular variant of PTC, the phenotype observed in the Tasmanian family, identified 17 such pedigrees, yielding a maximum hlod score of 4.17 and an NPL of 4.99 at markers in the 2q21 region. McKay et al. (2001) noted that loss of heterozygosity and cytogenetic studies had previously implicated 2q, and specifically 2q21, in NMTC.