Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers

Nikita Pozdeyev, Laurie M. Gay, Ethan S. Sokol, Ryan Hartmaier, Kelsi E. Deaver, Stephanie Davis, Jena D. French, Pierre Vanden Borre, Daniel V. LaBarbera, Aik-Choon Tan, Rebecca E. Schweppe, Lauren Fishbein, Jeffrey S. Ross, Bryan R. Haugen, Daniel W. Bowles

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance. Experimental Design: The genetic profiles of 583 advanced differentiated and 196 ATCs 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 with 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 thyroid cancers and ATCs. 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. An association of KDR, KIT, and PDGFRA amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown in vitro. Three genetically distinct types of ATCs 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.

Original languageEnglish
Pages (from-to)3059-3068
Number of pages10
JournalClinical Cancer Research
Volume24
Issue number13
DOIs
Publication statusPublished - 2018 Jul 1
Externally publishedYes

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Thyroid Neoplasms
Cytidine Deaminase
Immune Evasion
Vascular Endothelial Growth Factor Receptor-2
DNA Mismatch Repair
Monomeric GTP-Binding Proteins
Molecular Evolution
Neoplasm Genes
Receptor Protein-Tyrosine Kinases
Point Mutation
Genes
Anaplastic Thyroid Carcinoma
Neoplasms
Research Design
Pediatrics
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pozdeyev, N., Gay, L. M., Sokol, E. S., Hartmaier, R., Deaver, K. E., Davis, S., ... Bowles, D. W. (2018). Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clinical Cancer Research, 24(13), 3059-3068. https://doi.org/10.1158/1078-0432.CCR-18-0373

Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. / Pozdeyev, Nikita; Gay, Laurie M.; Sokol, Ethan S.; Hartmaier, Ryan; Deaver, Kelsi E.; Davis, Stephanie; French, Jena D.; Borre, Pierre Vanden; LaBarbera, Daniel V.; Tan, Aik-Choon; Schweppe, Rebecca E.; Fishbein, Lauren; Ross, Jeffrey S.; Haugen, Bryan R.; Bowles, Daniel W.

In: Clinical Cancer Research, Vol. 24, No. 13, 01.07.2018, p. 3059-3068.

Research output: Contribution to journalArticle

Pozdeyev, N, Gay, LM, Sokol, ES, Hartmaier, R, Deaver, KE, Davis, S, French, JD, Borre, PV, LaBarbera, DV, Tan, A-C, Schweppe, RE, Fishbein, L, Ross, JS, Haugen, BR & Bowles, DW 2018, 'Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers', Clinical Cancer Research, vol. 24, no. 13, pp. 3059-3068. https://doi.org/10.1158/1078-0432.CCR-18-0373
Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clinical Cancer Research. 2018 Jul 1;24(13):3059-3068. https://doi.org/10.1158/1078-0432.CCR-18-0373
Pozdeyev, Nikita ; Gay, Laurie M. ; Sokol, Ethan S. ; Hartmaier, Ryan ; Deaver, Kelsi E. ; Davis, Stephanie ; French, Jena D. ; Borre, Pierre Vanden ; LaBarbera, Daniel V. ; Tan, Aik-Choon ; Schweppe, Rebecca E. ; Fishbein, Lauren ; Ross, Jeffrey S. ; Haugen, Bryan R. ; Bowles, Daniel W. / Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 13. pp. 3059-3068.
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AU - Sokol, Ethan S.

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AU - Deaver, Kelsi E.

AU - Davis, Stephanie

AU - French, Jena D.

AU - Borre, Pierre Vanden

AU - LaBarbera, Daniel V.

AU - Tan, Aik-Choon

AU - Schweppe, Rebecca E.

AU - Fishbein, Lauren

AU - Ross, Jeffrey S.

AU - Haugen, Bryan R.

AU - Bowles, Daniel W.

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