Fusion Genes Linked to Metastasis after Thyroid Cancer
, by Maura Kate Costello, M.A.
According to previous studies, thyroid cancers diagnosed after childhood radiation exposure may be more aggressive, i.e., more likely to spread and form metastases. However, previous studies have not examined the molecular basis for this potential association. In a recent study, DCEG investigators determined that patients with papillary thyroid carcinomas (PTC), the most common thyroid cancer, that can be driven by gene fusions are more likely to present with cervical lymph node metastases at diagnosis than those with PTCs driven by point mutations. These observations explain previous reports because radiation exposure is associated with a greater likelihood of development of gene fusion drivers. These findings were published June 13, 2024, in the journal, Nature Communications, and were featured in the Editors’ Highlights by the journal’s editorial team.
Lindsay Morton, Ph.D., director of the Radiation Epidemiology Branch, led an interdisciplinary team of investigators from DCEG, the Institute of Endocrinology and Metabolism in Ukraine, and other colleagues to analyze the genomic and transcriptomic profiles of 440 tumor samples collected from individuals who developed PTC after exposure to radioactive fallout from the Chornobyl nuclear power plant accident in 1986. The researchers found that, while radiation was associated with occurrence of fusions, it did not have an independent effect on the frequency of metastases. Furthermore, the samples from the metastases and the primary tumors had very similar genetic profiles, but differed in their gene expression, most notably for a cluster of genes on chromosome 12, providing promising clues for future work to better understand the biologic basis for development of cervical lymph node metastases in PTC.
A novel aspect of the study was the ability to correlate genomic changes with patient and clinical characteristics, including radiation exposure. Because these factors are interrelated, it was important to construct a statistical model to evaluate the effect of each one independently. This study was made possible by the dedication of our colleagues in Ukraine, who have treated these patients and stored samples and clinical data over many years, and the visionary scientists who helped to set up the Chornobyl Tissue Bank in the 1990s.
Reference
Morton LM, Lee OW, Karyadi DM, ... Chanock SJ. Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident. Nat Commun. 2024.