Year: 2019
Type: article
Study design: Observational Study
Abstract: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.
DOI: 10.17615/fjw5-7e46
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The Human Genome Sequencing Center, Harvard Genome Characterization Center, Cancer transcriptome characterization using massively parallel DNA sequencing, G9000009266, G9000022338, G9000036768, G9000037270, G9000111900, G9000130770, G9000134271, G9000134348, G9000197591, G9000244592, G9000339650, G9000343359, G9000351369
OpenAlex ID: W4298316967