Image: A histopathology micrograph of anaplastic thyroid carcinoma (Photo courtesy of The Clayman Thyroid Cancer Center).
Anaplastic thyroid cancer (ATC) is a form of thyroid cancer, which has a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. Its anaplastic cells have poor differentiation, including dedifferentiation.
A new study has defined the genetic landscape of advanced differentiated and anaplastic thyroid cancer and identified genetic alterations of potential diagnostic, prognostic and therapeutic significance.
Scientists at the University of Colorado Cancer Center (Aurora, CO, USA) and their colleagues recently completed the largest-ever study of thyroid cancer genetics, mining the data of 583 patient samples of advanced differentiated thyroid cancer and 196 anaplastic thyroid cancers. Genetic profiles were generated and analyzed with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT (Memorial Sloan Kettering Cancer Center, New York, NY, USA) and FoundationOne (Foundation Medicine, Cambridge, MA, USA).
The investigators found that patients with 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 Apolipoprotein B mRNA Editing Catalytic Polypeptide (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 CDKN2A and CDKN2B, amplification of CCNE1, amplification of receptor tyrosine kinase genes KDR, KIT and PDGFRA, amplification of immune evasion genes CD274, PDCD1LG2 and JAK2 and activating point mutations in small GTPase RAC1 were associated with ATC.
Nikita Pozdeyev, MD, PhD, an assistant professor and lead author of the study, said, “Genetic analysis of early-stage thyroid cancers is most often not necessary as we successfully treat these tumors with surgery and radioactive iodine. But with distant metastases, genetic information becomes important for treatment. Because oncologists had sought this genetic information, our study is enriched for advanced cases.” The study was published on April 3, 2018, in the journal Clinical Cancer Research.
University of Colorado Cancer Center
Memorial Sloan Kettering Cancer Center