Telomere biology: Implications for radiation carcinogenesis

.Evidence has been accumulated to challenge the mutation theory for carcinogenesis, a major idea about a cause of cancer. The mutation theory starts from initiation, a mutation of a critical gene, being followed by promotion, which stimulates proliferation of the initiated cells. A majority of tumors, especially solid tumors, exhibits chromosomal instability characterized by random structural aberrations and ploidy changes. So far, no responsible gene has been found to account for chromosomal instability. Instead of the mutation theory, we introduce the telomere dysfunction theory for radiation carcinogenesis. In this model, a mutation of a critical gene is not presumed for initiation. Here, we demonstrate that radiation contributes to the induction of telomeric instability, which may lead to breakage–fusion–bridge cycle that potentially drives genome rearrangements. We propose that telomere dysfunction initiates and promotes chromosomal instability that plays a crucial role in an early step in radiation carcinogenesis.