The broad, long term objective of this project is to reduce morbidity and mortality caused by papillary thyroid carcinoma (PTC) which accounts for >80% of all thyroid cancers. PTC displays high heritability suggesting the existence of genes that when mutated predispose to PTC. So far no such inherited gene has been dentified. In preliminary experiments, linkage analysis in affected families has been used to discover several loci in the genome that likely harbor such genes. The first goal of this research is to refine the ocalization of these putative genes by linkage analysis and allelic association analysis using high-throughput technology. Once the loci have been narrowed to at most several megabases of DNA, positional cloning and mutation screening will be used to pinpoint the predisposing gene mutations. The discovery of genes predisposing to PTC would make it possible to predict who is, and who is not at high risk to develop PTC, allowing clinical screening and early detection, leading to public health benefits. Moreover, the elucidation of the genetic pathways leading to PTC allows therapeutic drugs and preventative strategies to be designed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA124570-05
Application #
8378695
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
2013-04-29
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2012
Total Cost
$276,251
Indirect Cost
$79,022
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Gudmundsson, Julius; Thorleifsson, Gudmar; Sigurdsson, Jon K et al. (2017) A genome-wide association study yields five novel thyroid cancer risk loci. Nat Commun 8:14517
Azmat, Umal; Porter, Kyle; Senter, Leigha et al. (2017) Thyroglobulin Liquid Chromatography-Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies. Thyroid 27:74-80
Chen, Hannah H; Händel, Norman; Ngeow, Joanne et al. (2017) Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells. J Allergy Clin Immunol 139:607-620.e15
Rossfeld, Kara K; Justiniano, Steven E; Ding, Haiming et al. (2017) Biological Evaluation of a Fluorescent-Imaging Agent for Medullary Thyroid Cancer in an Orthotopic Model. J Clin Endocrinol Metab 102:3268-3277
Saporito, Donika; Brock, Pamela; Hampel, Heather et al. (2017) Penetrance of a rare familial mutation predisposing to papillary thyroid cancer. Fam Cancer :
Byrd, Victoria; Getz, Ted M; Padmanabhan, Roshan et al. (2017) Microbiome in PTEN hamartoma tumor syndrome. Endocr Relat Cancer :
Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya et al. (2017) Variants in microRNA genes in familial papillary thyroid carcinoma. Oncotarget 8:6475-6482
Ni, Ying; Seballos, Spencer; Fletcher, Benjamin et al. (2017) Germline compound heterozygous poly-glutamine deletion in USF3 may be involved in predisposition to heritable and sporadic epithelial thyroid carcinoma. Hum Mol Genet 26:243-257
Ashtekar, Amruta; Huk, Danielle; Magner, Alexa et al. (2017) Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype. Endocr Relat Cancer 24:579-591

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