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Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):E8379-E8386. doi: 10.1073/pnas.1608461113. Epub 2016 Dec 12.

Molecular profiling of single circulating tumor cells from lung cancer patients.

Park SM1,2, Wong DJ3, Ooi CC4, Kurtz DM2,5,6, Vermesh O1,2, Aalipour A1,2, Suh S7, Pian KL8, Chabon JJ9, Lee SH10, Jamali M1, Say C11, Carter JN11, Lee LP10, Kuschner WG12,13, Schwartz EJ14, Shrager JB15, Neal JW6,16, Wakelee HA6,16, Diehn M9,11,16,17, Nair VS18,13,17, Wang SX19,8,17, Gambhir SS18,2,17.

Author information

1
Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305.
2
Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305.
3
Department of Electrical Engineering, Stanford University, Stanford, CA 94305.
4
Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
5
Department of Bioengineering, Stanford University, Stanford, CA 94305.
6
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
7
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
8
Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305.
9
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
10
Department of Bioengineering, University of California, Berkeley, CA 94720.
11
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305.
12
Section of Pulmonary and Critical Care Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304.
13
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
14
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
15
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305.
16
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305.
17
Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94305.
18
Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305; sgambhir@stanford.edu viswamnair@stanford.edu sxwang@stanford.edu.
19
Department of Electrical Engineering, Stanford University, Stanford, CA 94305; sgambhir@stanford.edu viswamnair@stanford.edu sxwang@stanford.edu.

Abstract

Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.

KEYWORDS:

circulating tumor cells; microfluidics; rare-cell sorting; reverse transcription-PCR; single-cell analysis

PMID:
27956614
PMCID:
PMC5206556
DOI:
10.1073/pnas.1608461113
[Indexed for MEDLINE]
Free PMC Article

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