Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice

摘要: Aged humans sustain a high rate of epithelial cancers such as carcinomas the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas lymphomas. Among many factors that may contribute to this species variance are differences in telomere length regulation. Telomeres comprise nucleoprotein complexes cap ends eukaryotic chromosomes maintained by reverse transcriptase, telomerase1. In human cells, insufficient levels telomerase lead attrition with cell division culture2 possibly ageing tumorigenesis vivo3,4,5. contrast, critical reduction is not observed mouse owing promiscuous expression long telomeres6,7,8,9,10. Here we provide evidence telomerase-deficient p53 mutant promotes development process fusion-bridge breakage leads formation complex non-reciprocal translocations—a classical cytogenetic feature carcinomas. Our data suggest model which dysfunction brought about continual renewal during life generates massive ploidy changes associated cancers.