Tumorigenesis in mice carrying a truncating Brca1 mutation.
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 the Brca1(tr/tr) mutation was apparently a late participant.
Ludwig
T
T
Department of Anatomy and Cell Biology, Columbia University, New York, New York 10032, USA. tl54@columbia.edu
Fisher
P
P
Ganesan
S
S
Efstratiadis
A
A
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D005260:Female; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion
D019313:BRCA1 Protein