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04-08-2017 | CNS metastases | Article

Molecular characterization of breast cancer CTCs associated with brain metastasis

Journal:
Nature Communications

Authors: Debasish Boral, Monika Vishnoi, Haowen N. Liu, Wei Yin, Marc L. Sprouse, Antonio Scamardo, David S. Hong, Tuan Z. Tan, Jean P. Thiery, Jenny C. Chang, Dario Marchetti

Publisher: Nature Publishing Group UK

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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