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

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s41467-024-49292-z.pdf (2.25 MB)

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ICR Authors

Berrington de Gonzalez, Amy

Authors

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

Document Type

Journal Article

Date

2024-06-13

Date Accepted

2024-05-23

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.

Citation

Nature Communications, 2024, 15 (1), pp. 5053 -

DOI

10.1038/s41467-024-49292-z
10.1038/s41467-024-49292-z

URI

https://repository.icr.ac.uk/handle/internal/6379

Rights

http://creativecommons.org/licenses/by/4.0/

Source Title

Nature Communications

Publisher

NATURE PORTFOLIO

ISSN

2041-1723

eISSN

2041-1723
2041-1723

Collections

Other ICR Research

Research Team

Clinical Cancer Epidemiol

Notes