title: Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21.
abstract: The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic 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 common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 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, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.
authors: International Agency for Research on Cancer, 69372 Lyon, cedex 08, France.
authors: J D
authors: JD
authors: McKay
authors: F
authors: F
authors: Lesueur
authors: L
authors: L
authors: Jonard
authors: A
authors: A
authors: Pastore
authors: J
authors: J
authors: Williamson
authors: L
authors: L
authors: Hoffman
authors: J
authors: J
authors: Burgess
authors: A
authors: A
authors: Duffield
authors: M
authors: M
authors: Papotti
authors: M
authors: M
authors: Stark
authors: H
authors: H
authors: Sobol
authors: B
authors: B
authors: Maes
authors: A
authors: A
authors: Murat
authors: H
authors: H
authors: Kääriäinen
authors: M
authors: M
authors: Bertholon-Grégoire
authors: M
authors: M
authors: Zini
authors: M A
authors: MA
authors: Rossing
authors: M E
authors: ME
authors: Toubert
authors: F
authors: F
authors: Bonichon
authors: M
authors: M
authors: Cavarec
authors: A M
authors: AM
authors: Bernard
authors: A
authors: A
authors: Boneu
authors: F
authors: F
authors: Leprat
authors: O
authors: O
authors: Haas
authors: C
authors: C
authors: Lasset
authors: M
authors: M
authors: Schlumberger
authors: F
authors: F
authors: Canzian
authors: D E
authors: DE
authors: Goldgar
authors: G
authors: G
authors: Romeo
mesh_terms: D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006042:Goiter / Q000453:epidemiology / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D018709:Statistics, Nonparametric; D013648:Tasmania / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D015534:Trans-Activators