Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing.
Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing.
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DOI：
10.1016/j.cell.2018.03.041
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发表时间：
2018-05-03
期刊：
影响因子：
64.5
通讯作者：
Navin NE
中科院分区：
文献类型：
--
作者：
Kim C;Gao R;Sei E;Brandt R;Hartman J;Hatschek T;Crosetto N;Foukakis T;Navin NE
三阴性乳腺癌(TNBC)是一种侵袭性亚型，常对化疗产生耐药性。一个悬而未决的问题是，抗性是由选择稀有的预先存在的克隆引起的，还是通过获得新的基因组异常而引起的。为了研究这个问题，我们在新辅助化疗(NAC)期间应用了单细胞DNA和RNA测序以及整体外显子组测序来分析来自20名TNBC患者的纵向样本。深层外显子组测序确定了10名NAC导致克隆消失的患者和10名治疗后克隆持续存在的患者。在8名患者中，我们进行了更详细的研究，使用单细胞DNA测序分析了900个细胞，使用单细胞RNA测序分析了6862个细胞。我们的数据显示，耐药的基因类型是预先存在的，并由NAC适应性地选择，而在TNBC患者中，转录谱是通过对化疗的响应而重新编程获得的。
Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy. An unresolved question is whether resistance is caused by the selection of rare pre-existing clones or alternatively through the acquisition of new genomic aberrations. To investigate this question, we applied single cell DNA and RNA sequencing in addition to bulk exome sequencing to profile longitudinal samples from 20 TNBC patients during neoadjuvant chemotherapy (NAC). Deep-exome sequencing identified 10 patients where NAC led to clonal extinction and 10 patients where clones persisted after treatment. In 8 patients, we performed a more detailed study using single cell DNA sequencing to analyze 900 cells and single cell RNA sequencing to analyze 6,862 cells. Our data showed that resistant genotypes were pre-existing and adaptively selected by NAC, while transcriptional profiles were acquired by reprogramming in response to chemotherapy in TNBC patients.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3
作者：
do Valle ÍF;Giampieri E;Simonetti G;Padella A;Manfrini M;Ferrari A;Papayannidis C;Zironi I;Garonzi M;Bernardi S;Delledonne M;Martinelli G;Remondini D;Castellani G
通讯作者：
Castellani G
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
30.8
作者：
Gao, Ruli;Davis, Alexander;McDonald, Thomas O.;Sei, Emi;Shi, Xiuqing;Wang, Yong;Tsai, Pei-Ching;Casasent, Anna;Waters, Jill;Zhang, Hong;Meric-Bernstam, Funda;Michor, Franziska;Navin, Nicholas E.
通讯作者：
Navin, Nicholas E.
DOI：
10.1126/science.aad7038
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Habib N;Li Y;Heidenreich M;Swiech L;Avraham-Davidi I;Trombetta JJ;Hession C;Zhang F;Regev A
通讯作者：
Regev A