Journal article

Modeling Breast Cancer Using CRISPR-Cas9-Mediated Engineering of Human Breast Organoids

Johanna F Dekkers, James R Whittle, Francois Vaillant, Huei-Rong Chen, Caleb Dawson, Kevin Liu, Maarten H Geurts, Marco J Herold, Hans Clevers, Geoffrey J Lindeman, Jane E Visvader

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | OXFORD UNIV PRESS INC | Published : 2020

Abstract

Breast cancer is characterized by histological and functional heterogeneity, posing a clinical challenge for patient treatment. Emerging evidence suggests that the distinct subtypes reflect the repertoire of genetic alterations and the target cell. However, the precise initiating events that predispose normal epithelium to neoplasia are poorly understood. Here, we demonstrate that breast epithelial organoids can be generated from human reduction mammoplasties (12 out of 12 donors), thus creating a tool to study the clonal evolution of breast cancer. To recapitulate de novo oncogenesis, we exploited clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 for targeted knockout ..

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Grants

Awarded by National Health and Medical Research Council, Australia


Awarded by Breast Cancer Research Foundation


Awarded by NHMRC Research Fellowships


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council, Australia (NHMRC 1113133, 1143105, 1145728, 1153049); NHMRC IRIISS; Victorian State Government Operational Infrastructure Support; Cancer Council Victoria Venture Grant; Australian Cancer Research Foundation; Breast Cancer Research Foundation (BCRF-18-182); and Joan Marshall Breast Cancer Research Fund. JRW was supported by an NHMRC/NBCF Research Fellowship and the Royal Australasian College of Physicians. JFD was supported by a Marie Sklodowska-Curie European Fellowship, and MJH (1156095), GJL (1078730), and JEV (1037230) were supported by NHMRC Research Fellowships.