Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident.
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Date
2024-06-13ICR Author
Author
Morton, LM
Lee, OW
Karyadi, DM
Bogdanova, TI
Stewart, C
Hartley, SW
Breeze, CE
Schonfeld, SJ
Cahoon, EK
Drozdovitch, V
Masiuk, S
Chepurny, M
Zurnadzhy, LY
Dai, J
Krznaric, M
Yeager, M
Hutchinson, A
Hicks, BD
Dagnall, CL
Steinberg, MK
Jones, K
Jain, K
Jordan, B
Machiela, MJ
Dawson, ET
Vij, V
Gastier-Foster, JM
Bowen, J
Mabuchi, K
Hatch, M
Berrington de Gonzalez, A
Getz, G
Tronko, MD
Thomas, GA
Chanock, SJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Thyroid Cancer, Papillary
Chernobyl Nuclear Accident
Lymphatic Metastasis
Male
Adult
Female
Thyroid Neoplasms
Mutation
Iodine Radioisotopes
Adolescent
Proto-Oncogene Proteins B-raf
Young Adult
Lymph Nodes
Proto-Oncogene Proteins c-ret
Child
Genomics
Middle Aged
Homeodomain Proteins
Gene Expression Profiling
MicroRNAs
Neoplasms, Radiation-Induced
Neck
Gene Expression Regulation, Neoplastic
Research team
Clinical Cancer Epidemiol
Language
eng
Date accepted
2024-05-23
License start date
2024-06-13
Citation
Nature Communications, 2024, 15 (1), pp. 5053 -
Publisher
NATURE PORTFOLIO