This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Reference
- Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers.
- Paper ID
- COSP45225
- Authors
- Affiliation
- Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus nikitapozdeyev@gmail.com.
- Journal
-
Clinical cancer research : an official journal of the American Association for Cancer Research, 2018
ISSN: 1078-0432
PMID: 29615459 (view at PubMed or Europe PMC) - Abstract
- Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer and identify genetic alterations of potential diagnostic, prognostic and therapeutic significance.The genetic profiles of 583 advanced differentiated and 196 anaplastic thyroid cancers (ATC) generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed.Results: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared to other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated and anaplastic thyroid cancers. Copy number losses and mutations of <i>CDKN2A</i> and <i>CDKN2B</i>, amplification of <i>CCNE1</i>, amplification of receptor tyrosine kinase genes <i>KDR, KIT</i> and <i>PDGFRA</i>, amplification of immune evasion genes <i>CD274, PDCD1LG2</i> and <i>JAK2</i> and activating point mutations in small GTPase <i>RAC1</i> were associated with ATC. An association of <i>KDR, KIT</i> and <i>PDGFRA</i> amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown <i>in vitro</i> Three genetically distinct types of ATC are proposed.Conclusions: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed.
- Paper Status
- Curated