TY - JOUR
T1 - An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer
AU - Johnson, Brett E.
AU - Creason, Allison L.
AU - Stommel, Jayne M.
AU - Keck, Jamie M.
AU - Parmar, Swapnil
AU - Betts, Courtney B.
AU - Blucher, Aurora
AU - Boniface, Christopher
AU - Bucher, Elmar
AU - Burlingame, Erik
AU - Camp, Todd
AU - Chin, Koei
AU - Eng, Jennifer
AU - Estabrook, Joseph
AU - Feiler, Heidi S.
AU - Heskett, Michael B.
AU - Hu, Zhi
AU - Kolodzie, Annette
AU - Kong, Ben L.
AU - Labrie, Marilyne
AU - Lee, Jinho
AU - Leyshock, Patrick
AU - Mitri, Souraya
AU - Patterson, Janice
AU - Riesterer, Jessica L.
AU - Sivagnanam, Shamilene
AU - Somers, Julia
AU - Sudar, Damir
AU - Thibault, Guillaume
AU - Weeder, Benjamin R.
AU - Zheng, Christina
AU - Nan, Xiaolin
AU - Thompson, Reid F.
AU - Heiser, Laura M.
AU - Spellman, Paul T.
AU - Thomas, George
AU - Demir, Emek
AU - Chang, Young Hwan
AU - Coussens, Lisa M.
AU - Guimaraes, Alexander R.
AU - Corless, Christopher
AU - Goecks, Jeremy
AU - Bergan, Raymond
AU - Mitri, Zahi
AU - Mills, Gordon B.
AU - Gray, Joe W.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/2/15
Y1 - 2022/2/15
N2 - 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.
AB - 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.
KW - human tumor atlas
KW - metastatic breast cancer
KW - personalized medicine
KW - precision oncology
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U2 - 10.1016/j.xcrm.2022.100525
DO - 10.1016/j.xcrm.2022.100525
M3 - Article
C2 - 35243422
AN - SCOPUS:85124502976
SN - 2666-3791
VL - 3
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 2
M1 - 100525
ER -