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Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident

Author

Listed:
  • Lindsay M. Morton

    (National Institutes of Health)

  • Olivia W. Lee

    (National Institutes of Health)

  • Danielle M. Karyadi

    (National Institutes of Health)

  • Tetiana I. Bogdanova

    (V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine)

  • Chip Stewart

    (Broad Institute of MIT and Harvard)

  • Stephen W. Hartley

    (National Institutes of Health)

  • Charles E. Breeze

    (National Institutes of Health)

  • Sara J. Schonfeld

    (National Institutes of Health)

  • Elizabeth K. Cahoon

    (National Institutes of Health)

  • Vladimir Drozdovitch

    (National Institutes of Health)

  • Sergii Masiuk

    (National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine)

  • Mykola Chepurny

    (National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine)

  • Liudmyla Yu Zurnadzhy

    (V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine)

  • Jieqiong Dai

    (Frederick National Laboratory for Cancer Research)

  • Marko Krznaric

    (Charing Cross Hospital)

  • Meredith Yeager

    (Frederick National Laboratory for Cancer Research)

  • Amy Hutchinson

    (Frederick National Laboratory for Cancer Research)

  • Belynda D. Hicks

    (Frederick National Laboratory for Cancer Research)

  • Casey L. Dagnall

    (Frederick National Laboratory for Cancer Research)

  • Mia K. Steinberg

    (Frederick National Laboratory for Cancer Research)

  • Kristine Jones

    (Frederick National Laboratory for Cancer Research)

  • Komal Jain

    (Frederick National Laboratory for Cancer Research)

  • Ben Jordan

    (Frederick National Laboratory for Cancer Research)

  • Mitchell J. Machiela

    (National Institutes of Health)

  • Eric T. Dawson

    (National Institutes of Health
    Nvidia Corporation)

  • Vibha Vij

    (National Institutes of Health)

  • Julie M. Gastier-Foster

    (Biospecimen Core Resource
    Ohio State University College of Medicine)

  • Jay Bowen

    (Biospecimen Core Resource)

  • Kiyohiko Mabuchi

    (National Institutes of Health)

  • Maureen Hatch

    (National Institutes of Health)

  • Amy Berrington de Gonzalez

    (National Institutes of Health)

  • Gad Getz

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Mykola D. Tronko

    (V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine)

  • Gerry A. Thomas

    (Charing Cross Hospital)

  • Stephen J. Chanock

    (National Institutes of Health)

Abstract

Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.

Suggested Citation

  • Lindsay M. Morton & Olivia W. Lee & Danielle M. Karyadi & Tetiana I. Bogdanova & Chip Stewart & Stephen W. Hartley & Charles E. Breeze & Sara J. Schonfeld & Elizabeth K. Cahoon & Vladimir Drozdovitch , 2024. "Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49292-z
    DOI: 10.1038/s41467-024-49292-z
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    References listed on IDEAS

    as
    1. Yilong Li & Nicola D. Roberts & Jeremiah A. Wala & Ofer Shapira & Steven E. Schumacher & Kiran Kumar & Ekta Khurana & Sebastian Waszak & Jan O. Korbel & James E. Haber & Marcin Imielinski & Joachim We, 2020. "Patterns of somatic structural variation in human cancer genomes," Nature, Nature, vol. 578(7793), pages 112-121, February.
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    3. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
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