The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer
The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer
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DOI：
10.1158/1078-0432.ccr-05-1029
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发表时间：
2006-02-15
影响因子：
11.5
通讯作者：
Borresen-Dale, AL
中科院分区：
文献类型：
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作者：
Olivier, M;Langerod, A;Borresen-Dale, AL
为了探讨TP53体细胞突变在乳腺癌中的临床价值，我们收集了1794例长期随访的原发性乳腺癌患者的临床和分子数据，这些患者的肿瘤已通过基因测序筛选TP53外显子5至8突变。TP53突变在导管和髓质型、侵袭型（高级别、大尺寸、淋巴结阳性、激素受体含量低）和10岁以上的女性肿瘤中更为常见；P < 0.0001)。TP53突变的预后价值与肿瘤大小、淋巴结状态和激素受体含量无关，证实并协调了先前在较小系列中的发现。此外，TP53突变与孕激素受体（PR）状态之间存在相互作用，TP53突变合并孕激素受体缺失与最差预后相关。尽管先前的研究强调dna结合基序内的错义突变比这些基序外的错义突变预后更差，但我们发现非错义突变与dna结合基序内的错义突变具有类似的预后价值。然而，特异性错义突变（密码子179和R248W）似乎与更糟糕的预后相关。这些结果是迄今为止分析的最大的序列，表明通过基因测序鉴定的TP53突变在乳腺癌中具有独立的预后价值，并可能在临床实践中具有潜在的用途。
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 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.