p53 mutation with frequent novel codons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours

摘要: The status of p53 was investigated in breast tumours arising germ-line carriers mutant alleles BRCA1 and BRCA2 a control series sporadic tumours. expression detected 20/26 (77%) BRCA1-, 10/22 (45%) BRCA2-associated 25/72 (35%) grade-matched Analysis sequence revealed that the gene 33/50 (66%) BRCA-associated tumours, whereas 7/20 contained mutation (P<0.05). A number mutations have not been previously described human cancer databases, whilst others occur extremely rarely. additional genes, p16INK4, Ki-ras beta-globin absence or very low incidence mutations, suggesting higher frequency does reflect generalized increase susceptibility to acquisition somatic mutation. Furthermore, frameshift polypurine tracts present coding TGF beta type II receptor (TGF IIR) Bax implies loss function confer mutator phenotype such as found with microsatellite instability (MSI). p21Waf1 expressed regardless and, furthermore, some expressing wild-type did express detectable p21Waf1. These data do support, therefore, simple model based on studies BRCA-/- embryos, which results deregulated proliferation. Rather, they imply proliferation will be subject multiple mechanisms growth regulation.