title: p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis.
abstract: We determined the pattern of mutations in exons 2-11 and adjacent intronic regions in breast cancers from Midwestern US white women. Twenty-one mutations were detected in 53 tumors (39.6%). Comparisons of the pattern of mutations within exons 5-9 showed that the frequency of missense mutations (44%) was lower in breast cancers of US Midwestern women than in most tumor types including breast cancers in other populations. Compared to breast cancers reported in a Scottish population, US women had a high frequency of G:C-->T:A transversions (P = 0.046). These findings suggest that environmental or endogenous factors contribute to p53 mutagenesis in mammary tissue to different extents among different populations. With a median follow-up of 19 months, the presence of a mutation was associated with shorter time to disease recurrence (P = 0.05) and shorter survival (P = 0.003). Putative dominant negative missense-type mutations (missense and in-frame microdeletions; P = 0.001) and null mutations (hemizygous nonsense and frameshift mutations; P = 0.007) were equally ominous. Thus, tumors with missense p53 mutations resulting in over-expression of a dysfunctional but otherwise intact protein have a clinical outcome similar to tumors with null mutations resulting in a truncated or garbled protein.
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: J
authors.initials: J
authors.lastname: Cunningham
authors.forename: E M
authors.initials: EM
authors.lastname: De Vries
authors.forename: R M
authors.initials: RM
authors.lastname: McGovern
authors.forename: J J
authors.initials: JJ
authors.lastname: Schroeder
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: H
authors.initials: H
authors.lastname: Blaszyk
authors.forename: L E
authors.initials: LE
authors.lastname: Wold
authors.forename: D
authors.initials: D
authors.lastname: Schaid
authors.forename: S S
authors.initials: SS
authors.lastname: Sommer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D017384:Sequence Deletion; D014481:United States / Q000453:epidemiology
chemical_list: D004273:DNA, Neoplasm