Transcriptomic but not genomic variability confers phenotype of breast cancer stem cells

查看全文 作　　者：Mengying [1]Tong;Ziqian [1,2]Deng;Mengying [1]Yang;Chang [1]Xu;Xiaolong [1]Zhang;Qingzheng [1]Zhang;Yuwei [1]Liao;Xiaodi [1]Deng;Dekang [1]Lv;Xuehong [1]Zhang;Yu [1]Zhang;Peiying [1]Li;Luyao [1]Song;Bicheng [2,3]Wang;Aisha Al-[1]Dherasi;Zhiguang [1]Li;Quentin [1,2]Liu

机构地区：[1]Center of Genome and Personalized Medicine,Institute of Cancer Stem Cell,Dalian Medical University,Dalian 116044,Liaoning,P.R.China;[2]State Key Laboratory of Oncology in South China,Collaborative Innovation Center of Cancer Medicine,Sun Yat-sen University Cancer Center,Guangzhou,Guang-dong 510060,P.R.China;[3]Cancer Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,P.R.China

出　　处：《Cancer Communications》索引2018年第38卷第1期,共16页

基　　金：supported by Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China(No.IRT_17R15);National Natural Science Foundation of China(Nos.81630005 to QL,81573025 to QL,81472637 to ZL,81672784 to ZL,and 81602200 to DL);Innovative Research Team in University of Liaoning(No.LT2017001 to QL);The program for climbing Scholars of Liaoning,Dalian High-level Talent Innovation Program(2016RD12 to QL);International Scientific and Technological Cooperation of Dalian(2015F11GH095 to QL). 摘　　要：Background:Breast cancer stem cells(BCSCs)are considered responsible for cancer relapse and drug resistance.Understanding the identity of BCSCs may open new avenues in breast cancer therapy.Although several discoveries have been made on BCSC characterization,the factors critical to the origination of BCSCs are largely unclear.This study aimed to determine whether genomic mutations contribute to the acquisition of cancer stem-like phenotype and to investigate the genetic and transcriptional features of BCSCs.Methods:We detected potential BCSC phenotype-associated mutation hotspot regions by using whole-genome sequencing on parental cancer cells and derived serial-generation spheres in increasing order of BCSC frequency,and then performed target deep DNA sequencing at bulk-cell and single-cell levels.To identify the transcriptional program associated with BCSCs,bulk-cell and single-cell RNA sequencing was performed.Results:By using whole-genome sequencing of bulk cells,potential BCSC phenotype-associated mutation hotspot regions were detected.Validation by target deep DNA sequencing,at both bulk-cell and single-cell levels,revealed no genetic changes specifically associated with BCSC phenotype.Moreover,single-cell RNA sequencing showed profound transcriptomic variability in cancer cells at the single-cell level that predicted BCSC features.Notably,this transcriptomic variability was enriched during the transcription of 74 genes,revealed as BCSC markers.Breast cancer patients with a high risk of relapse exhibited higher expression levels of these BCSC markers than those with a low risk of relapse,thereby highlighting the clinical significance of predicting breast cancer prognosis with these BCSC markers.Conclusions:Transcriptomic variability,not genetic mutations,distinguishes BCSCs from non-BCSCs.The identified 74 BCSC markers have the potential of becoming novel targets for breast cancer therapy. 关键词：Breast cancer Cancer stem cell GENOMICS SEQUENCING TRANSCRIPTOMICS

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Transcriptomic but not genomic variability confers phenotype of breast cancer stem cells

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