Only missense mutations affecting the DNA binding domain of p53 influence outcomes in patients with breast carcinoma.
Only missense mutations affecting the DNA binding domain of p53 influence outcomes in patients with breast carcinoma.
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DOI：
10.1371/journal.pone.0055103
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lizard-Nacol S
中科院分区：
文献类型：
--
作者：
Végran F;Rebucci M;Chevrier S;Cadouot M;Boidot R;Lizard-Nacol S
TP53 基因突变的存在会影响肿瘤对某些治疗的反应，尤其是乳腺癌。在这项研究中，我们分析了 206 名乳腺癌患者的 p53 mRNA 表达、17p13 的 LOH 以及外显子 2 至 11 的 TP53 突变，并将结果与无病生存率和总生存率相关联。观察到的突变根据其在三个蛋白质结构域（反式激活结构域、DNA 结合结构域、寡聚化结构域）中的类型和位置进行分类，并与无病生存和总体生存相关。在我们的人群中，p53 mRNA 表达和 LOH 均与结果无关。关于 TP53 突变，27% 的肿瘤发生突变 (53/197)，TP53 基因突变的存在与较差的总生存期相关 (p = 0.0026)，但与无病生存期无关 (p = 0.0697)，中位生存期分别为 80 个月和 78 个月。当改变被分为突变类别和位置并与生存相关时，除了 P53 DNA 结合域中的错义突变外，携带突变的肿瘤与野生型肿瘤具有相同的生存概况。关于 DNA 结合域的错义突变，中位无病生存期和总生存期分别为 23 个月和 35 个月（分别为 p = 0.0021 和 p<0.0001），而突变肿瘤的总体生存期为 78 个月和 80 个月。这项工作表明，TP53 移码突变或寡聚化结构域错义突变患者的无病生存率和总生存率与野生型 TP53 患者相同。
The presence of a TP53 gene mutation can influence tumour response to some treatments, especially in breast cancer. In this study, we analysed p53 mRNA expression, LOH at 17p13 and TP53 mutations from exons 2 to 11 in 206 patients with breast carcinoma and correlated the results with disease-free and overall survival. The observed mutations were classified according to their type and location in the three protein domains (transactivation domain, DNA binding domain, oligomerization domain) and correlated with disease-free and overall survival. In our population, neither p53 mRNA expression nor LOH correlated with outcome. Concerning TP53 mutations, 27% of tumours were mutated (53/197) and the presence of a mutation in the TP53 gene was associated with worse overall survival (p = 0.0026) but not with disease-free survival (p = 0.0697), with median survival of 80 months and 78 months, respectively. When alterations were segregated into mutation categories and locations, and related to survival, tumours harbouring mutations other than missense mutations in the DNA binding domain of P53 had the same survival profiles as wild-type tumours. Concerning missense mutations in the DNA binding domain, median disease-free and overall survival was 23 months and 35 months, respectively (p = 0.0021 and p<0.0001, respectively), compared with 78 and 80 months in mutated tumours overall. This work shows that disease-free and overall survival in patients with a frameshift mutation of TP53 or missense mutation in the oligomerization domain are the same as those in wild-type TP53 patients.
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影响因子：
50.3
作者：
Jackson JG;Pant V;Li Q;Chang LL;Quintás-Cardama A;Garza D;Tavana O;Yang P;Manshouri T;Li Y;El-Naggar AK;Lozano G
通讯作者：
Lozano G
影响因子：
11.5
作者：
Olivier, M;Langerod, A;Borresen-Dale, AL
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Borresen-Dale, AL
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作者：
Aramayo R;Sherman MB;Brownless K;Lurz R;Okorokov AL;Orlova EV
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Orlova EV
影响因子：
158.5
作者：
Poeta, M. Luana;Manola, Judith;Koch, Wayne M.
通讯作者：
Koch, Wayne M.
影响因子：
82.9
作者：
BERGH, J;NORBERG, T;HOLMBERG, L
通讯作者：
HOLMBERG, L