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

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, Sergii Masiuk, Mykola Chepurny, Liudmyla Yu Zurnadzhy, Jieqiong Dai, Marko Krznaric, Meredith Yeager, Amy Hutchinson, Belynda D. Hicks, Casey L. Dagnall, Mia K. Steinberg, Kristine Jones, Komal Jain, Ben Jordan, Mitchell J. Machiela, Eric T. Dawson, Vibha Vij, Julie M. Gastier-Foster, Jay Bowen, Kiyohiko Mabuchi, Maureen Hatch, Amy Berrington de Gonzalez, Gad Getz, Mykola D. Tronko, Gerry A. Thomas and Stephen J. Chanock ()
Additional contact information
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
Vibha Vij: National Institutes of Health
Julie M. Gastier-Foster: Biospecimen Core Resource
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
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

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49292-z

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