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.
Nikiforov
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Department of Pathology, University of Cincinnatti, OH 45267-0529, USA. Yuri.Nikiforov@uc.edu
D005796:Genes / Q000235:genetics; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011839:Radiation, Ionizing; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases