title: Mapping a new familial thyroid epithelial neoplasia susceptibility locus to chromosome 8p23.1-p22 by high-density single-nucleotide polymorphism genome-wide linkage analysis.
abstract: BACKGROUND
  Familial nonmedullary thyroid carcinoma (FNMTC) accounts for approximately 5% of all thyroid tumors. Genetic mapping studies have identified four different chromosomal regions predisposing to FNMTC: fPTC/PRN (1p13.2-1q22), NMTC1 (2q21), MNG1 (14q32), and TCO (19p13.2).
  
  
  OBJECTIVE
  Our objective was to map the gene predisposing to familial thyroid epithelial neoplasia in a large Portuguese family.
  
  
  RESULTS
  The clinical screening of a Portuguese family identified 11 members affected with benign thyroid lesions and five affected with thyroid carcinomas. Linkage analysis excluded the involvement of the fPTC/PRN, NMTC1, MNG1, and TCO loci. To map the gene predisposing to thyroid epithelial neoplasia in this family, a genome-wide linkage analysis was conducted, using DNA samples from 17 family members and high-density single-nucleotide polymorphism arrays. A genome-wide significant evidence of linkage, to a single region on chromosome 8p23.1-p22 was obtained, with a maximum parametric haplotype-based LOD score of 4.41 (theta=0.00). Linkage analysis with microsatellite markers confirmed linkage to 8q23.1-p22, and recombination events delimited the minimal region to a 7.46-Mb span. Seventeen suggestive candidate genes located in the minimal region were excluded as susceptibility genes by mutational analysis. Allelic losses in the 8p23.1-p22 region were absent in seven thyroid tumors from family members, suggesting that the inactivation of a putative tumor suppressor gene may have occurred through other mechanisms.
  
  
  CONCLUSIONS
  Our results present evidence for the existence of a novel familial thyroid epithelial neoplasia susceptibility locus on chromosome 8p23.1-p22, providing the basis for the identification of a gene for this disease.
authors.affiliation: Centro de Investigação de Patobiologia Molecular (CIPM), Serviço de Endocrinoligia, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, Portugal. bcavaco@ipolisboa.min-saude.pt
authors.forename: Branca M
authors.initials: BM
authors.lastname: Cavaco
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Batista
authors.forename: Luís G
authors.initials: LG
authors.lastname: Sobrinho
authors.forename: Valeriano
authors.initials: V
authors.lastname: Leite