The overall goal of this project is to use genetics to improve our chances of preventing, predicting, diagnosing, treating and curing papillary thyroid carcinoma (PTC), which accounts for >80% of all thyroid cancers. Thus far, traditional genetic approaches have failed to pinpoint the culpable predisposing genes. Two genome wide association studies (GWAS) identified five genetic loci associated with highly significant low penetrance predisposition with strong population impact. Two of the pinpointed SNPs reside in conventional translated genes that are pursued elsewhere. Here we focus on the three loci (one in 9q22 and two in 14q13) that are not associated with known genes. Using molecular and in silico methods we have narrowed the regions in which the culpable genomic mutations must reside. In both cases we have identified and delineated novel long intergenic noncoding RNA (lincRNA) genes. These are implicated in the genetic predisposition as shown by their dramatic loss of expression in tumor tissue. These lincRNAs genes are the focus of the first aim of this project. Much more needs to be learned about the mechanistic aspects of the lincRNAs, moreover the culpable genomic mutations must be unequivocally identified.
The second aim focuses on translational studies examining the predictive and diagnostic value of the SNPs and the culpable mutations nearby, and their possible association with other genetic/genomic changes in PTC as well as clinical factors and outcome. Our preliminary work has shown that the five available risk SNPs are additive.
; The discovery of genes predisposing to PTC and their interaction with other genetic and clinical factors will allow for more accurate genetic counseling, genotype-based risk stratification, and prognostication. Moreover, the elucidation of the genetic pathways leading to PTC will allow therapeutic drugs and preventative strategies to be designed.
|Bagheri-Yarmand, Rozita; Sinha, Krishna M; Li, Ling et al. (2018) Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress-Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer. Mol Cancer Res :|
|Puli, Oorvashi Roy; Danysh, Brian P; McBeath, Elena et al. (2018) The Transcription Factor ETV5 Mediates BRAFV600E-Induced Proliferation and TWIST1 Expression in Papillary Thyroid Cancer Cells. Neoplasia 20:1121-1134|
|Abrams, Zachary B; Zucker, Mark; Wang, Min et al. (2018) Thirty biologically interpretable clusters of transcription factors distinguish cancer type. BMC Genomics 19:738|
|Shu, Yi; Yin, Hongran; Rajabi, Mehdi et al. (2018) RNA-based micelles: A novel platform for paclitaxel loading and delivery. J Control Release 276:17-29|
|He, Huiling; Li, Wei; Liyanarachchi, Sandya et al. (2018) The Role of NRG1 in the Predisposition to Papillary Thyroid Carcinoma. J Clin Endocrinol Metab 103:1369-1379|
|Chakedis, Jeffery; Shirley, Lawrence A; Terando, Alicia M et al. (2018) Identification of the Thoracic Duct Using Indocyanine Green During Cervical Lymphadenectomy. Ann Surg Oncol 25:3711-3717|
|Xu, Congcong; Haque, Farzin; Jasinski, Daniel L et al. (2018) Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy. Cancer Lett 414:57-70|
|Segkos, Konstantinos; Porter, Kyle; Senter, Leigha et al. (2018) Neck Ultrasound in Patients with Follicular Thyroid Carcinoma. Horm Cancer 9:433-439|
|Wang, Yanqiang; He, Huiling; Liyanarachchi, Sandya et al. (2018) The role of SMAD3 in the genetic predisposition to papillary thyroid carcinoma. Genet Med 20:927-935|
|Valenciaga, Anisley; Saji, Motoyasu; Yu, Lianbo et al. (2018) Transcriptional targeting of oncogene addiction in medullary thyroid cancer. JCI Insight 3:|
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