Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.
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Authors
Heindl, A
Khan, AM
Rodrigues, DN
Eason, K
Sadanandam, A
Orbegoso, C
Punta, M
Sottoriva, A
Lise, S
Banerjee, S
Yuan, Y
Khan, AM
Rodrigues, DN
Eason, K
Sadanandam, A
Orbegoso, C
Punta, M
Sottoriva, A
Lise, S
Banerjee, S
Yuan, Y
Document Type
Journal Article
Date
2018-09-25
Date Accepted
2018-08-15
Abstract
How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to define cancer morphological diversification within the spatial context of the microenvironment. Tumor spatial zones, where cancer cell nuclei diversify in shape, are mapped in each tumor. Integration of this spatially explicit analysis with omics and clinical data reveals a relationship between morphological diversification and the dysregulation of DNA repair, loss of nuclear integrity, and increased disease mortality. Within the Immunoreactive subtype, spatial analysis further reveals significantly lower lymphocytic infiltration within diversified zones compared with other tumor zones, suggesting that even immune-hot tumors contain cells capable of immune escape. Our findings support a model whereby a subpopulation of morphologically plastic cancer cells with dysregulated DNA repair promotes ovarian cancer progression through positive selection by immune evasion.
Citation
Nature communications, 2018, 9 (1), pp. 3917 - ?
Source Title
Publisher
NATURE RESEARCH
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Computational Pathology & Integrated Genomics
Systems and Precision Cancer Medicine
Systems and Precision Cancer Medicine