Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Apr 24

PMID 29681456

Citations 521

Authors

Charissa Kim

Ruli Gao

Emi Sei

Rachel Brandt

Johan Hartman

Thomas Hatschek

Nicola Crosetto

Theodoros Foukakis

Nicholas E Navin

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy. An unresolved question is whether resistance is caused by the selection of rare pre-existing clones or alternatively through the acquisition of new genomic aberrations. To investigate this question, we applied single-cell DNA and RNA sequencing in addition to bulk exome sequencing to profile longitudinal samples from 20 TNBC patients during neoadjuvant chemotherapy (NAC). Deep-exome sequencing identified 10 patients in which NAC led to clonal extinction and 10 patients in which clones persisted after treatment. In 8 patients, we performed a more detailed study using single-cell DNA sequencing to analyze 900 cells and single-cell RNA sequencing to analyze 6,862 cells. Our data showed that resistant genotypes were pre-existing and adaptively selected by NAC, while transcriptional profiles were acquired by reprogramming in response to chemotherapy in TNBC patients.

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