Spatial positioning of RET and H4 following radiation exposure leads to tumor development.

Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many others. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a large increase in incidence of thyroid cancer was observed in children exposed to radiation after the Chernobyl nuclear accident. A high prevalence of chromosomal rearrangements involving the RET gene was found among these radiation-induced thyroid tumors. As a result of such rearrangement, a portion of the RET gene is fused with another gene, typically with the H4 or ELE1 . However, since the DNA targets of ionizing radiation are randomly distributed throughout the cell nucleus, the reason for predilection for the RET rearrangements in thyroid cells was unclear.