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Abstract
The enumeration of EpCAM-positive circulating tumor cells (CTCs) has allowed estimation of overall metastatic burden in breast cancer patients. However, a thorough understanding of CTCs associated with breast cancer brain metastasis (BCBM) is necessary for early identification and evaluation of treatment response to BCBM. Here we report that BCBM CTCs is enriched in a distinct sub-population of cells identifiable by their biomarker expression and mutational content. Deriving from a comprehensive analysis of CTC transcriptomes, we discovered a unique “circulating tumor cell gene signature” that is distinct from primary breast cancer tissues. Further dissection of the circulating tumor cell gene signature identified signaling pathways associated with BCBM CTCs that may have roles in potentiating BCBM. This study proposes CTC biomarkers and signaling pathways implicated in BCBM that may be used either as a screening tool for brain micro-metastasis detection or for making rational treatment decisions and monitoring therapeutic response in patients with BCBM.
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Details
1 Biomarker Research Program Center, Houston Methodist Research Institute, Houston,, TX, USA
2 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston,, TX, USA
3 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
4 Institute for Academic Medicine, Houston Methodist Hospital, Houston,, TX, USA
5 Biomarker Research Program Center, Houston Methodist Research Institute, Houston,, TX, USA; Institute for Academic Medicine, Houston Methodist Hospital, Houston,, TX, USA