A susceptibility locus for papillary thyroid carcinoma on chromosome 8q24. Cancer Res 2009 Jan 15;69(2):625-31
Date
01/17/2009Pubmed ID
19147577Pubmed Central ID
PMC2634601DOI
10.1158/0008-5472.CAN-08-1071Scopus ID
2-s2.0-58349088314 (requires institutional sign-in at Scopus site) 126 CitationsAbstract
Papillary thyroid carcinoma (PTC) displays higher heritability than most other cancers. To search for genes predisposing to PTC, we performed a genome-wide linkage analysis in a large family with PTC and melanoma. Among several peaks the highest was at 8q24, with a maximum nonparametric linkage (NPL) score of 7.03. Linkage analysis was then broadened to comprise 25 additional PTC families that produced a maximum NPL score of 3.2, P = 0.007 at the 8q24 locus. Fine mapping with microsatellite markers was compatible with linkage to the 8q24 locus in 10 of the 26 families. In the large family, a approximately 320 Kb haplotype was shared by individuals with PTC, melanoma, or benign thyroid disease, but not by unaffected individuals. A 12 Kb haplotype of 8 SNP markers within the larger haplotype was shared by 9 of the 10 families in which the 8q24 locus was compatible with linkage. The shared haplotype is located within 2 known overlapping protein-coding genes, thyroglobulin (TG) and Src-like adaptor (SLA). Resequencing of the coding and control regions of TG and SLA did not disclose putative mutations in PTC patients. Embedded in the TG-SLA region are three likely noncoding RNA genes, one of which (AK023948) harbors the 8-SNP haplotype. Resequencing of AK023948 and one of the other RNA genes did not reveal candidate mutations. Gene expression analysis indicated that AK023948 is significantly down-regulated in most PTC tumors. The putative noncoding RNA gene AK023948 is a candidate susceptibility gene for PTC.
Author List
He H, Nagy R, Liyanarachchi S, Jiao H, Li W, Suster S, Kere J, de la Chapelle AMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingCarcinoma, Papillary
Chromosomes, Human, Pair 8
Female
Gene Expression Profiling
Genetic Linkage
Genetic Predisposition to Disease
Genome, Human
Haplotypes
Humans
Male
Melanoma
Multigene Family
Pedigree
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins pp60(c-src)
Thyroglobulin
Thyroid Neoplasms
