Tumorigenesis in mice carrying a truncating Brca1 mutation
- 1Department of Anatomy and Cell Biology, and 2Department of Pathology, Columbia University, New York, New York 10032 USA; 3Dana-Farber Cancer Institute, Boston, Massachusetts 02115 USA; 4Department of Genetics and Development, and 5Institute of Cancer Genetics, Columbia University, New York, New York, 10032 USA
Abstract
We generated mouse mutants carrying in the Brca1 locus a modification (Brca1 tr) that eliminates the C-terminal half of the protein product and obtained results indicating that, depending on genetic background, the missing BRCT and/or other domains are dispensable for survival, but essential for tumor suppression. Most of the apparently hypomorphic Brca1 tr/tr mutants developed various tumors. Lymphomas were detected at all ages, whereas sarcomas and carcinomas, including breast cancer, appeared after a long latency. The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which theBrca1 tr/tr mutation was apparently a late participant.
