Repository series · ncbi-prjeb5127

Identifying Molecular Signature of Saudi Thyroid Cancer Using Next Generation Sequencing Technology Based on International Cancer Genome Consortium (ICGC) Guidelines

Although papillary thyroid cancer constitutes a significant health burden in Saudi Arabia, it is a poorly understood tumor and this tumor type is largely under- researched. Thyroid cancer is the most common endocrine malignancy and differentiated thyroid cancer (DTC), which includes papillary (PTC) and follicular (FTC) subtypes, accounts for 90% of all thyroid malignancies In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries (GCC) also. Most patients with DTC do well with traditional therapy which includes total thyroidectomy, radioiodine ablation (RAI) and thyroid hormone suppression. However, some will go on to develop progressive disease that is not amenable to further surgery and/or not responsive to RAI. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. We aim to analyze the genomic DNA sequences of 500 thyroid cancers and the corresponding DNA from blood. With the goal of a better understanding the pathobiology of thyroid carcinogenesis we will use state of the art "deep sequencing" technology to decipher the molecular and genetic signature of Saudi PTC. The development of next-generation (NextGen) sequencing technologies has spurred high hopes for the identification of novel biomarkers for disease diagnosis, prognosis, and prediction, including thyroid cancer. Our objectives will be achieved through the following aims: the studies of specific aim 1 will be the generation of comprehensive catalogues of genomic abnormalities (somatic mutations) in thyroid cancer of the papillary thyroid carcinoma histology subtype which is of clinical and social importance in Saudi Arabia. Specific aim 2 will catalogue for each papillary thyroid carcinoma to include the full range of somatic mutations including single-nucleotide variants, insertions, deletions, copy number changes, translocations and other chromosomal rearrangements. Specific aim 3 will generate complementary catalogues of transcriptomic and epigenomic datasets from selected tumor cases that demonstrate abnormalities from aim 1 and 2. The outcome of this study will provide a better understanding of PTC and should have important clinical implications, as it could result in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC tumors.