An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer

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; Joe W Gray

doi:10.1016/j.xcrm.2022.100525

An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer

Cell Rep Med. 2022 Feb 15;3(2):100525. doi: 10.1016/j.xcrm.2022.100525.

Authors

Brett E Johnson^{1

2}, Allison L Creason^{1

2}, Jayne M Stommel^{1

2}, Jamie M Keck¹, Swapnil Parmar¹, Courtney B Betts^{1

3}, Aurora Blucher^{1

3}, Christopher Boniface^{2

4}, Elmar Bucher², Erik Burlingame^{2

5}, Todd Camp¹, Koei Chin^{1

2}, Jennifer Eng², Joseph Estabrook^{1

6}, Heidi S Feiler^{1

2}, Michael B Heskett⁶, Zhi Hu^{1

2}, Annette Kolodzie¹, Ben L Kong^{1

7}, Marilyne Labrie^{1

3}, Jinho Lee¹, Patrick Leyshock¹, Souraya Mitri¹, Janice Patterson^{1

8}, Jessica L Riesterer^{2

9}, Shamilene Sivagnanam^{1

3

5}, Julia Somers^{1

6}, Damir Sudar¹⁰, Guillaume Thibault², Benjamin R Weeder², Christina Zheng¹, Xiaolin Nan^{2

4}, Reid F Thompson^{2

11}, Laura M Heiser^{1

2}, Paul T Spellman^{2

6}, George Thomas^{1

12}, Emek Demir^{1

6}, Young Hwan Chang^{2

5}, Lisa M Coussens^{1

3}, Alexander R Guimaraes^{1

13}, Christopher Corless^{7

12}, Jeremy Goecks^{1

2}, Raymond Bergan¹⁴, Zahi Mitri^{15

16}, Gordon B Mills^{1

3}, Joe W Gray^{1

2}

Affiliations

¹ Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
² Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA.
³ Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
⁴ Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR 97239, USA.
⁵ Computational Biology Program, Oregon Health & Science University, Portland, OR 97239, USA.
⁶ Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA.
⁷ Department of Pharmacy Services, Oregon Health & Science University, Portland, OR 97239, USA.
⁸ Knight Diagnostic Laboratories, Oregon Health & Science University, Portland, OR 97239, USA.
⁹ Multiscale Microscopy Core, Oregon Health & Science University, Portland, OR 97239, USA.
¹⁰ Quantitative Imaging Systems LLC, Portland, OR 97239, USA.
¹¹ Division of Hospital and Specialty Medicine, VA Portland Healthcare System, Portland, OR 97239, USA.
¹² Department of Pathology & Laboratory Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
¹³ Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR 97239, USA.
¹⁴ Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
¹⁵ Division of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
¹⁶ Department of Medicine, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.

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.

Keywords: human tumor atlas; metastatic breast cancer; personalized medicine; precision oncology.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Biopsy
Breast Neoplasms* / genetics
Female
Humans
Tumor Microenvironment / genetics

Abstract

Publication types

MeSH terms

Grants and funding