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TP53 mutations and breast cancer prognosis: Particularly poor survival rates for cases with mutations in the zinc‐binding domains
Author(s) -
Børresen AnneLise,
Andersen Tone Ikdahl,
Eyfjörd Jorunn E.,
Cornelis Renee S.,
Thorlacius Steinunn,
Borg Åke,
Johansson Ulla,
Theillet Charles,
Scherneck Siegfried,
Hartman Susanne,
Cornelisse Cees J.,
Hovig Eivind,
Devilee Peter
Publication year - 1995
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870140113
Subject(s) - missense mutation , breast cancer , mutation , cancer research , oncology , biology , medicine , disease , zinc finger , cancer , genetics , bioinformatics , gene , transcription factor
Acquired mutations in TP53 as well as immunohistochemically detectable protein expression have been implicated as prognostic factors for breast cancer. We have evaluated the relationship between mutations detected in 119 breast tumours and various clinicohistopathological indices, stratifying the mutations according to the functional domains as defined by the recent elucidation of the crystal structure of the protein. Patients with missense mutations located in regions encoding parts of the protein involved in zinc‐binding had significantly decreased disease‐free and overall survival relative to patients whose tumours had mutations in other domains. These results indicate that these biochemically defined domains also have biological relevance in terms of breast cancer disease course, and suggest that some mutations in TP53 , more than others, can contribute to the development of clinically more aggressive and perhaps treatment resistant breast tumours. When confirmed, this will be of potential importance in predicting the clinical behaviour of breast cancer and its responsiveness to therapy.