Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients.
Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients.
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DOI：
10.4143/crt.2017.598
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发表时间：
2019-01
影响因子：
4.6
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Deng L;Zhu X;Sun Y;Wang J;Zhong X;Li J;Hu M;Zheng H
PIK 3CA在中国乳腺癌患者中的患病率可能被低估。因此，我们调查了体细胞PIK 3CA/AKT 1突变在中国乳腺癌患者中的分布，并探讨其在肿瘤表型和疾病预后中的作用。前瞻性收集了2008年至2013年期间华西医院507例乳腺癌患者的肿瘤。使用新一代测序技术检测新鲜冷冻肿瘤中AKT 1和PIK 3CA的全外显子，并分析PIK 3CA/AKT 1突变与临床病理特征之间的相关性。AKT 1基因突变率为3.6%（18/507）。携带AKT 1突变的患者的肿瘤为雌激素受体（ER）+/孕激素受体（PR）+/人表皮生长因子受体2（HER 2）+，并且更可能具有Ki 67的高表达水平。PIK 3CA突变的患病率为46.5%（236/507），35例患者携带两种或三种PIK 3CA基因变体。PIK 3CA突变与ER+/PR+/HER 2+状态相关。具有PIK 3CA（或PIK 3CA/AKT 1）中的一个突变的患者的预后与具有野生型PIK 3CA（或PIK 3CA/AKT 1）的患者的预后没有显著差异，而具有PIK 3CA（或PIK 3CA/AKT 1）中的两个或三个变体的患者在整个组和所有三个亚组（ER+、HER 2+、Ki 67高）中表现出较差的预后，特别是在总生存期方面。在中国乳腺癌患者中检测到高频率的体细胞PIK 3CA突变。除了突变频率，PIK 3CA和AKT 1基因的肿瘤突变负担也应该引起关注，因为它们可能与预后不良相关。
The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed. The AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival. A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.
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影响因子：
3.8
作者：
Engels CC;Kiderlen M;Bastiaannet E;van Eijk R;Mooyaart A;Smit VT;de Craen AJ;Kuppen PJ;Kroep JR;van de Velde CJ;Liefers GJ
通讯作者：
Liefers GJ
影响因子：
--
作者：
Kim JY;Lee E;Park K;Park WY;Jung HH;Ahn JS;Im YH;Park YH
通讯作者：
Park YH
影响因子：
3.8
作者：
Cizkova M;Vacher S;Meseure D;Trassard M;Susini A;Mlcuchova D;Callens C;Rouleau E;Spyratos F;Lidereau R;Bièche I
通讯作者：
Bièche I
DOI：
10.1093/jnci/djt121
发表时间：
2013-07-03
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Loi S;Michiels S;Lambrechts D;Fumagalli D;Claes B;Kellokumpu-Lehtinen PL;Bono P;Kataja V;Piccart MJ;Joensuu H;Sotiriou C
通讯作者：
Sotiriou C
影响因子：
8.8
作者：
Cizkova M;Dujaric ME;Lehmann-Che J;Scott V;Tembo O;Asselain B;Pierga JY;Marty M;de Cremoux P;Spyratos F;Bieche I
通讯作者：
Bieche I