The Chernobyl nuclear disaster has caused a remarkable increase in radiation-induced papillary thyroid carcinoma in children and young adults. In this issue of the JCI, Ricarte-Filho and colleagues demonstrate that chromosomal rearrangements are the oncogenic “drivers” in most post-Chernobyl carcinomas and that they often lead to unscheduled activation of the MAPK signaling pathway. These findings represent a major step forward in our understanding of radiation-induced carcinogenesis and suggest various hypotheses about the mechanisms underlying the formation and selection of gene rearrangements during cancer cell evolution.
Most of them target components of the MAPK signaling cascade and include rearrangements of RET (RET/PTC) or NTRK1 and NTRK3 receptor tyrosine kinases (RTKs), or BRAF kinase. An exception is represented by rearrangements affecting the PPARG steroid hormone receptor.