Chernobyl-Linked Thyroid Cancers Have Distinct Genetic Fingerprints, Study Shows

Dr. Christopher Mason

The rearrangement of chromosomes marks thyroid cancers that developed in children exposed to the 1986 Chernobyl disaster, and appears to have "driven" the growth of those tumors, according to new research led by investigators at Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center.

Though the spike in pediatric thyroid cancers in the area surrounding the explosion of the nuclear reactor in Ukraine is well known — nine years after the disaster, cases jumped to 4 per 100,000 children, up from 0.03-0.05 cases per 100,000 in the region in 1995 — scientists haven't been able to determine the biological reason for many of the victims. A new study in the Journal of Clinical Investigation that compared thyroid tumors from radiation-exposed patients to those of other, non-exposed thyroid cancer patients shows unique genetic characteristics of the growths in children who lived near the site. The results point to potential ways that radiation can trigger these tumors, and underscore the need to quickly evacuate people — especially young children and adolescents — from any site of a radiation spill or accident to mitigate the risk of genetic damage.

"Our work shows the direct genetic impact of radiation exposure, and reveals the unique types of dangerous genetic damage that can be induced by radiation exposure," said Dr. Christopher Mason, an assistant professor in the Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine Institute at Weill Cornell.

Mason - along with Dr. James Fagin and colleagues at Sloan-Kettering, the Institute of Endocrinology and Metabolism in Kiev, Ukraine, and Imperial College in London - used a technique called RNA-sequencing to find fusions of genes in the tumors. They found that 84 percent of the thyroid cancer patients exposed to Chernobyl radiation had fusions of cancer-related genes, yet only 33 percent of patients who were not exposed to the disaster had those chromosomal rearrangements. The oncogene fusions disrupt the ability of cells to regulate their growth, which can lead to cancer, according to the study.

Drs. Mason and Fagin also examined the DNA from these patients by performing whole-genome sequencing of the tumors, which complemented their work in RNA-sequencing (which finds active mutations) to gauge the overall genetic impact of radiation on these patients' DNA. The scientists, including first authors Dr. Julio Ricarte-Filho and Sheng Li, found that the rate of mutations (single-base changes and small insertions and deletions of genetic code) across the whole genome was similar in radiation-exposed and non-exposed patients. So while most small mutations across the genome were either repaired or sustained equally in both groups, the risk of large rearrangements of chromosomes was far greater during radiation exposure and could have created genetic constructs that drive the cancer.

Previously, scientists thought that such constructs, called "fusion oncogenes," might have been equally present across all cancers. "These data challenge the notion that fusion oncogenes are about equally prevalent in pediatric thyroid cancers, regardless of whether or not they are radiation induced," the authors wrote in the study.

"Since many of our cancer-triggering genes were near each other on the rearranged chromosomes, this also shows that the structure of the genome is a risk factor for the fusion of these genes, which adds to our understanding of a three-dimensional, dynamic view of DNA during irradiation and the human genome's susceptibility for cancer," Mason added.

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