1. An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer
- Author
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Brett E. Johnson, Allison L. Creason, Jayne M. Stommel, Jamie M. Keck, Swapnil Parmar, Courtney B. Betts, Aurora Blucher, Christopher Boniface, Elmar Bucher, Erik Burlingame, Todd Camp, Koei Chin, Jennifer Eng, Joseph Estabrook, Heidi S. Feiler, Michael B. Heskett, Zhi Hu, Annette Kolodzie, Ben L. Kong, Marilyne Labrie, Jinho Lee, Patrick Leyshock, Souraya Mitri, Janice Patterson, Jessica L. Riesterer, Shamilene Sivagnanam, Julia Somers, Damir Sudar, Guillaume Thibault, Benjamin R. Weeder, Christina Zheng, Xiaolin Nan, Reid F. Thompson, Laura M. Heiser, Paul T. Spellman, George Thomas, Emek Demir, Young Hwan Chang, Lisa M. Coussens, Alexander R. Guimaraes, Christopher Corless, Jeremy Goecks, Raymond Bergan, Zahi Mitri, Gordon B. Mills, and Joe W. Gray
- Subjects
Biopsy ,Tumor Microenvironment ,Humans ,Breast Neoplasms ,Female ,General Biochemistry, Genetics and Molecular Biology - Abstract
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells and extrinsic microenvironmental influences change during treatment. To support the development of methods for identifying these mechanisms in individual people, here we present an omic and multidimensional spatial (OMS) atlas generated from four serial biopsies of an individual with metastatic breast cancer during 3.5 years of therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times and doses, anatomic imaging, and blood-based response measurements to clinical and exploratory analyses, which includes comprehensive DNA, RNA, and protein profiles; images of multiplexed immunostaining; and 2- and 3-dimensional scanning electron micrographs. These data report aspects of heterogeneity and evolution of the cancer genome, signaling pathways, immune microenvironment, cellular composition and organization, and ultrastructure. We present illustrative examples of how integrative analyses of these data reveal potential mechanisms of response and resistance and suggest novel therapeutic vulnerabilities.
- Published
- 2022
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