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Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer

Author

Listed:
  • Seong-Keun Yoo

    (Seoul National University
    Seoul National University
    Macrogen Inc.)

  • Young Shin Song

    (Seoul National University College of Medicine
    CHA University)

  • Eun Kyung Lee

    (National Cancer Center)

  • Jinha Hwang

    (Seoul National University Graduate School)

  • Hwan Hee Kim

    (Seoul National University College of Medicine)

  • Gyeongseo Jung

    (Seoul National University College of Medicine)

  • Young A Kim

    (Seoul National University Boramae Medical Center)

  • Su-jin Kim

    (Seoul National University College of Medicine)

  • Sun Wook Cho

    (Seoul National University College of Medicine)

  • Jae-Kyung Won

    (Seoul National University College of Medicine)

  • Eun-Jae Chung

    (Seoul National University College of Medicine)

  • Jong-Yeon Shin

    (Seoul National University
    Macrogen Inc.)

  • Kyu Eun Lee

    (Seoul National University
    Seoul National University College of Medicine)

  • Jong-Il Kim

    (Seoul National University
    Seoul National University Graduate School)

  • Young Joo Park

    (Seoul National University
    Seoul National University College of Medicine)

  • Jeong-Sun Seo

    (Seoul National University
    Macrogen Inc.
    Seoul National University Graduate School
    Seoul National University Bundang Hospital)

Abstract

Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAFV600E and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

Suggested Citation

  • Seong-Keun Yoo & Young Shin Song & Eun Kyung Lee & Jinha Hwang & Hwan Hee Kim & Gyeongseo Jung & Young A Kim & Su-jin Kim & Sun Wook Cho & Jae-Kyung Won & Eun-Jae Chung & Jong-Yeon Shin & Kyu Eun Lee , 2019. "Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10680-5
    DOI: 10.1038/s41467-019-10680-5
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    Cited by:

    1. Seong Eun Lee & Seongyeol Park & Shinae Yi & Na Rae Choi & Mi Ae Lim & Jae Won Chang & Ho-Ryun Won & Je Ryong Kim & Hye Mi Ko & Eun-Jae Chung & Young Joo Park & Sun Wook Cho & Hyeong Won Yu & June You, 2024. "Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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