Genetic instability favoring transversions associated with ErbB2-induced mammary tumorigenesis

摘要: It has been argued that genetic instability is required to generate the myriad mutations fuel tumor initiation and progression and, in fact, patients with heritable cancer susceptibility syndromes harbor defects specific genes normally maintain DNA integrity. However, vast majority of human cancers arise sporadically, absence deficiencies known “mutator” genes. We used a cII-based mutation detection assay show mean frequency forward primary mammary adenocarcinomas arising mouse virus-c-erbB2 transgenic mice harboring multiple copies λ bacteriophage genome was significantly higher than aged-matched, wild-type tissue. Analysis cII mutational spectrum within genomic demonstrated >6-fold elevation transversion frequency, resulting highly unusual inversion transition/transversion ratio characteristic normal epithelium; frameshift frequencies were unaltered. Arising oncogenic point c-erbB2 transgene such tumors predominantly transversions as well. Data from this model system support notion elaboration mutator phenotype consequential event breast suggest novel replication/repair gene relatively early target c-erbB2-induced tumorigenesis.