Integrated genomics of thyroid cancer

Abstract

Objective Advances in DNA sequencing technology have permitted comprehensive genomic characterization of the most common types of cancer, including those of the thyroid gland. The Cancer Genome Atlas (TCGA) program of the U.S. National Institutes of Health (a joint NCI and NHGRI effort) has performed the first of several attempts to define the genomic landscape of thyroid cancer by identifying the somatic genetic changes of a large cohort of papillary thyroid carcinoma (PTC). Methods The TCGA Research Network performed an integrated genomic analysis of nearly 500 PTCs, the most common type, using next generation DNA sequencing and other pan-genomic methods, together with detailed clinical and pathologic data. Results Despite significant pre-existing knowledge about the genetics of PTC, the TCGA project illuminated many novel aspects of the genetics of PTC. Novel driving alterations, both novel single nucleotide variants and gene fusions, were identified. Driving events were nearly mutually exclusive. Tumors were divided into BRAF-V600E-like and RAS-like groups based on their gene expression profiles and were shown to have distinct differentiation and signaling properties. Several differentially expressed miRs were identified and hypothesized to play a prognostic role in PTC. Discussion The overarching conclusion of this study is PTC is much more genetically diverse than previously recognized, with BRAF-driven tumors being genetically diverse and also fundamentally different from RAS-driven tumors.