Nature Communications (Jun 2024)
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,
- Stephen J. Chanock
Affiliations
- Lindsay M. Morton
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Olivia W. Lee
- Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Danielle M. Karyadi
- Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Tetiana I. Bogdanova
- Laboratory of Morphology of the Endocrine System, 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
- Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Charles E. Breeze
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Sara J. Schonfeld
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Elizabeth K. Cahoon
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Vladimir Drozdovitch
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 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
- Laboratory of Morphology of the Endocrine System, V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine
- Jieqiong Dai
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Marko Krznaric
- Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital
- Meredith Yeager
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Amy Hutchinson
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Belynda D. Hicks
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Casey L. Dagnall
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Mia K. Steinberg
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Kristine Jones
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Komal Jain
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Ben Jordan
- Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
- Mitchell J. Machiela
- Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Eric T. Dawson
- Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Vibha Vij
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Julie M. Gastier-Foster
- Nationwide Children’s Hospital, Biospecimen Core Resource
- Jay Bowen
- Nationwide Children’s Hospital, Biospecimen Core Resource
- Kiyohiko Mabuchi
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Maureen Hatch
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Amy Berrington de Gonzalez
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Gad Getz
- Broad Institute of MIT and Harvard
- Mykola D. Tronko
- Department of Fundamental and Applied Problems of Endocrinology, V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine
- Gerry A. Thomas
- Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital
- Stephen J. Chanock
- Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- DOI
- https://doi.org/10.1038/s41467-024-49292-z
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
