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

By Charissa R. Kim, Ruli Gao, Emi Sei, R. Brandt, Johan Hartman, T. Hatschek, N. Crosetto, T. Foukakis, N. Navin. Cell, 2018

942 citations recorded by the source corpus.

SUMMARY 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 where NAC led to clonal extinction and 10 patients where 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.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a06f4144be2602bbf6d07e6ad465e9fa1dd78435

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In Cancer Research

1. K. Polyak

In Molecular Biology

1. K. Polyak
2. R. Weinberg

In Oncology

1. A. Garrido-Castro
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3. R. Weinberg
4. D. Hanahan

Citations in the corpus

• Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment (2019, background): “Bulk exome and single-cell sequencing in a small number of pre– and post–neoadjuvant therapy samples suggest the occurrence of adaptive clonal extinction or persistence and acquired transcriptional reprogramming as potential models of chemoresistance (140).”
• Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. (2020, background): “In recent years, scRNA-seq appeared as a revolutionary technic for addressing intra-tumor cellular complexity (27,30,34-44).”