p53 gene mutations in breast cancers in midwestern US women: Null as well as missense-type mutations are associated with poor prognosis

S. Saitoh, J. Cunningham, E. M.G. De Vries, R. M. McGovern, J. J. Schroeder, A. Hartmann, H. Blaszyk, L. E. Wold, D. Schaid, S. S. Sommer, J. S. Kovach

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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 microdeletion mutations (P = 0.006) and a low 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 overexpression of a dysfunctional but otherwise intact protein have a clinical outcome similar to tumors with null mutations resulting in a truncated or garbled protein.

Original languageEnglish (US)
Pages (from-to)2869-2875
Number of pages7
JournalOncogene
Volume9
Issue number10
StatePublished - Oct 1 1994

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Saitoh, S., Cunningham, J., De Vries, E. M. G., McGovern, R. M., Schroeder, J. J., Hartmann, A., Blaszyk, H., Wold, L. E., Schaid, D., Sommer, S. S., & Kovach, J. S. (1994). p53 gene mutations in breast cancers in midwestern US women: Null as well as missense-type mutations are associated with poor prognosis. Oncogene, 9(10), 2869-2875.