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    The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer.

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    Authors
    Olivier, Magali
    Langerød, Anita
    Carrieri, Patrizia
    Bergh, Jonas
    Klaar, Sigrid
    Eyfjord, Jorunn
    Theillet, Charles
    Rodriguez, Carmen
    Lidereau, Rosette
    Bièche, Ivan
    Varley, Jennifer
    Bignon, Yves-Jean
    Uhrhammer, Nancy
    Winqvist, Robert
    Jukkola-Vuorinen, Arja
    Niederacher, Dieter
    Kato, Shunsuke
    Ishioka, Chikashi
    Hainaut, Pierre
    Børresen-Dale, Anne-Lise
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    Affiliation
    IARC, Lyon, France.
    Issue Date
    2006-02-15
    
    Metadata
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    Abstract
    To investigate the clinical value of somatic TP53 mutations in breast cancer, we assembled clinical and molecular data on 1,794 women with primary breast cancer with long-term follow-up and whose tumor has been screened for mutation in exons 5 to 8 of TP53 by gene sequencing. TP53 mutations were more frequent in tumors of ductal and medullar types, aggressive phenotype (high grade, large size, node positive cases, and low hormone receptor content) and in women <60 years old. TP53 mutations within exons 5 to 8 conferred an elevated risk of breast cancer-specific death of 2.27 (relative risk >10 years; P < 0.0001) compared with patients with no such mutation. The prognostic value of TP53 mutation was independent of tumor size, node status, and hormone receptor content, confirming and reconciling previous findings in smaller series. Moreover, an interaction between TP53 mutation and progesterone receptor (PR) status was revealed, TP53 mutation combined with the absence of progesterone receptor being associated with the worst prognosis. Whereas previous studies have emphasized the fact that missense mutations in the DNA-binding motifs have a worse prognosis than missense mutations outside these motifs, we show that non-missense mutations have prognostic value similar to missense mutations in DNA-binding motifs. Nonetheless, specific missense mutants (codon 179 and R248W) seem to be associated with an even worse prognosis. These results, obtained on the largest series analyzed thus far, show that TP53 mutations identified by gene sequencing have an independent prognostic value in breast cancer and could have potential uses in clinical practice.
    Citation
    The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. 2006, 12 (4):1157-67 Clin. Cancer Res.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/72748
    DOI
    10.1158/1078-0432.CCR-05-1029
    PubMed ID
    16489069
    Type
    Article
    Language
    en
    ISSN
    1078-0432
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.CCR-05-1029
    Scopus Count
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    All Paterson Institute for Cancer Research

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