American Association for Cancer Research (AACR)

Clinical Cancer Research

, volume 24 , issue 13 , pages 3059-3068

Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers

Nikita Pozdeyev ^{1, 2, 3}

Laurie M. Gay ⁴

Ethan S Sokol ⁴

Ryan Hartmaier ⁴

Kelsi E Deaver ¹

Stephanie Davis ^{1, 5}

Jena D. French ^{1, 3}

Pierre Vanden Borre ⁴

Daniel V Labarbera ^{3, 6}

Aik Choon Tan ^{3, 7}

Rebecca E. Schweppe ^{1, 3}

Lauren Fishbein ^{1, 2, 3}

Jeffrey S. Ross ^{4, 8}

Bryan R. Haugen ^{1, 3}

Daniel W. Bowles ^{3, 7}

Hide authors affiliations Show authors affiliations: 8 affiliations

1Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. |

2Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. |

6Department of Pharmaceutical Sciences, Skaags School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado. |

⁴

7Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. |

⁵

3University of Colorado Cancer Center, Aurora, Colorado. |

⁶

4Foundation Medicine Inc., Cambridge, Massachusetts. |

⁷

5Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado |

⁸

8Departments of Pathology and Urology, Upstate Medical University, Syracuse, New York. |

Publication type: Journal Article

Publication date: 2018-07-01

American Association for Cancer Research (AACR)

Clinical Cancer Research

scimago Q1

wos Q1

SJR: 4.800

CiteScore: 19.0

Impact factor: 10.2

ISSN: 10780432, 15573265

DOI: 10.1158/1078-0432.ccr-18-0373

Copy DOI

PubMed ID: 29615459

Cancer Research

Oncology

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. Clin Cancer Res; 24(13); 3059–68. ©2018 AACR.

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424

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GOST |

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GOST Copy

Pozdeyev N. et al. Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers // Clinical Cancer Research. 2018. Vol. 24. No. 13. pp. 3059-3068.

GOST all authors (up to 50) Copy

Pozdeyev N., Gay L. M., Sokol E. S., Hartmaier R., Deaver K. E., Davis S., French J. D., Borre P. V., Labarbera D. V., Tan A. C., Schweppe R. E., Fishbein L., Ross J. S., Haugen B. R., Bowles D. W. Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers // Clinical Cancer Research. 2018. Vol. 24. No. 13. pp. 3059-3068.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1158/1078-0432.ccr-18-0373

UR - https://doi.org/10.1158/1078-0432.ccr-18-0373

TI - Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers

T2 - Clinical Cancer Research

AU - Pozdeyev, Nikita

AU - Gay, Laurie M.

AU - Sokol, Ethan S

AU - Hartmaier, Ryan

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.

PY - 2018

DA - 2018/07/01

PB - American Association for Cancer Research (AACR)

SP - 3059-3068

IS - 13

VL - 24

PMID - 29615459

SN - 1078-0432

SN - 1557-3265

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2018_Pozdeyev,

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

title = {Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers},

journal = {Clinical Cancer Research},

year = {2018},

volume = {24},

publisher = {American Association for Cancer Research (AACR)},

month = {jul},

url = {https://doi.org/10.1158/1078-0432.ccr-18-0373},

number = {13},

pages = {3059--3068},

doi = {10.1158/1078-0432.ccr-18-0373}

}

MLA

Cite this

MLA Copy

Pozdeyev, Nikita, et al. “Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers.” Clinical Cancer Research, vol. 24, no. 13, Jul. 2018, pp. 3059-3068. https://doi.org/10.1158/1078-0432.ccr-18-0373.

Publisher

American Association for Cancer Research (AACR)

Journal

Clinical Cancer Research

scimago Q1

wos Q1

SJR

4.800

CiteScore

19.0

Impact factor

10.2

ISSN

10780432 (Print)

15573265 (Electronic)