Molecular profiling of single circulating tumor cells from lung cancer patients

Seung Min Park(Stanford University), Dawson J. Wong(Stanford University), Chin Chun Ooi(Stanford University), David M. Kurtz(Stanford University), Ophir Vermesh(Stanford University), Amin Aalipour(Stanford University), Susie Suh(University School), Kelsey L. Pian(Stanford University), Jacob J. Chabon(Stanford University), Sang Hun Lee(University of California, Berkeley), Mehran Jamali(Stanford University), Carmen Say(Stanford University), Justin N. Carter(Stanford University), Luke P. Lee(University of California, Berkeley), Ware G. Kuschner(VA Palo Alto Health Care System), Erich Schwartz(Stanford University), Joseph B. Shrager(Stanford University), Joel W. Neal(Stanford University), Heather A. Wakelee(Stanford University), Maximilian Diehn(Palo Alto University), Viswam S. Nair(Palo Alto University), Shan X. Wang(Palo Alto University), Sanjiv S. Gambhir(Palo Alto University)
Proceedings of the National Academy of Sciences
December 12, 2016
Cited by 99Open Access
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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.


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