机构：[1]California NanoSystems Institute, Crump Institute for Molecular Imaging, Departmentof Molecular and Medical Pharmacology, University of California, Los Angeles,Los Angeles, CA 90095, USA[2]Beijing National Laboratory for Molecular Sciences,MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Collegeof Chemistry and Molecular Engineering, Peking University, Beijing 100871, China[3]Urologic Oncology Program and Uro-Oncology Research Laboratories, SamuelOschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles,CA 90048, USA[4]State Key Laboratory of Medicinal Chemical Biology, College ofPharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University,Tianjin 300353, China[5]Smart Organic Materials Laboratory, Institute of Chemistry,Academia Sinica, Taipei 11529, Taiwan[6]Department of Pathology, GuangdongProvincial Hospital of Traditional Chinese Medicine, Guangzhou University of ChineseMedicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou510120, China大德路总院珠海院区病理科病理科大德路总院病理科广东省中医院[7]Department of Surgery, University of California, Los Angeles, LosAngeles, CA 90095, USA[8]Research Center for Applied Sciences, Academia Sinica,Taipei 11529, Taiwan[9]Department of Pediatrics, David Geffen School of Medicine,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, andChildren’s Discovery and Innovation Institute, University of California, Los Angeles,Los Angeles, CA 90095, USA[10]California NanoSystems Institute, Departments ofChemistry and Biochemistry and Materials Science and Engineering, University ofCalifornia, Los Angeles, Los Angeles, CA 90095, USA
Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA. Here, we demonstrate a covalent chemistry-based nanostructured silicon substrate ("Click Chip") for CTC purification that leverages bioorthogonal ligation-mediated CTC capture and disulfide cleavage-driven CTC release. This platform is ideal for CTC mRNA assays because of its efficient, specific, and rapid purification of pooled CTCs, enabling downstream molecular quantification using reverse transcription Droplet Digital polymerase chain reaction. Rearrangements of ALK/ROS1 were quantified using CTC mRNA and matched with those identified in biopsy specimens from 12 patients with late-stage non-small cell lung cancer. Moreover, CTC counts and copy numbers of ALK/ROS1 rearrangements could be used together for evaluating treatment responses and disease progression.
基金：
National Institutes of Health (R33CA174562,
R44CA180482, R01CA218356, U01CA198900, and R21CA235340). J.D. gratefully
acknowledges financial support from the China Scholarship Council (201706010064).
基金编号：R33CA174562,R44CA180482, R01CA218356, U01CA198900, and R21CA235340
第一作者机构：[1]California NanoSystems Institute, Crump Institute for Molecular Imaging, Departmentof Molecular and Medical Pharmacology, University of California, Los Angeles,Los Angeles, CA 90095, USA[2]Beijing National Laboratory for Molecular Sciences,MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Collegeof Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
通讯作者：
推荐引用方式(GB/T 7714)：
Jiantong Dong,Yu Jen Jan,Ju Cheng,et al.Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells[J].SCIENCE ADVANCES.2019,5(7):doi:10.1126/sciadv.aav9186.
APA：
Jiantong Dong,Yu Jen Jan,Ju Cheng,Ryan Y. Zhang,Meng Meng...&Yazhen Zhu.(2019).Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells.SCIENCE ADVANCES,5,(7)
MLA：
Jiantong Dong,et al."Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells".SCIENCE ADVANCES 5..7(2019)
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