Objective: Recent advances in next-generation sequencing (NGS) technology have permitted comprehensive genomic characterization of the most common types of cancer. The Cancer Genome Atlas (TCGA), a program of the U.S. National Institutes of Health (a joint NCI and NHGRI effort), was created to systematically analyze the genome of the most common types of cancer, including the most common type of thyroid cancer, papillary thyroid carcinoma (PTC). TCGA has performed the first of several large-scale attempts to define the genomic landscape of thyroid cancer by identifying the somatic genetic alterations of a significant cohort of PTC.
Methods: The TCGA Research Network completed an integrated genomic analysis of 496 PTCs using NGS and other pan-genomic technologies, together with detailed pathologic and clinical data.
Results: Significant knowledge was known about the genetics of PTC. However, the comprehensive nature of the TCGA project revealed many novel aspects of the genetics and epigenetics of PTC. Mutually exclusive novel single nucleotide variants and gene fusions, thought to be driving events, were identified. Based on gene expression profiles, PTCs were divided into BRAF-V600E-like and RAS-like groups, which displayed distinct differentiation and signaling properties. Differentially expressed miRs were identified and several were hypothesized to play a prognostic role in PTC.
Discussion: This study revealed many novel genetics alterations in the PTC genome. However, the primary conclusion of this study is PTC represents a genetically diverse group of neoplasms, with BRAF-driven tumours being most diverse and also fundamentally different from RAS-driven tumors.