This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by He, H. Articles by de la Chapelle, A. Search for Related Content PubMed PubMed Citation Articles by He, H. Articles by de la Chapelle, A.

A Susceptibility Locus for Papillary Thyroid Carcinoma on Chromosome 8q24

¹ Human Cancer Genetics Program, Comprehensive Cancer Center; ² Department of Pathology, The Ohio State University, Columbus, Ohio; and ³ Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

Requests for reprints: Albert de la Chapelle, The Ohio State University, 420 West 12th Avenue, Ste 646 TMRF 420, Columbus, OH 43210. Phone: 614-688-4781; Fax: 614-688-4772; E-mail: albert.delachapelle{at}osumc.edu.

Key Words: papillary thyroid carcinoma • susceptibility locus • haplotype sharing • noncoding RNA gene

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 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 suseptibility gene for PTC. [Cancer Res 2009;69(2):625–31]

This article has been cited by other articles:

				P. P. Amaral, C. Neyt, S. J. Wilkins, M. E. Askarian-Amiri, S. M. Sunkin, A. C. Perkins, and J. S. Mattick Complex architecture and regulated expression of the Sox2ot locus during vertebrate development RNA, November 1, 2009; 15(11): 2013 - 2027. [Abstract] [Full Text] [PDF]