Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity

Andreas Heindl, Adnan Mujahid Khan, Daniel Nava Rodrigues, Katherine Eason, Anguraj Sadanandam, Cecilia Orbegoso, Marco Punta, Andrea Sottoriva, Stefano Lise, Susana Banerjee and Yinyin Yuan ()
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Andreas Heindl: The Institute of Cancer Research
Adnan Mujahid Khan: The Institute of Cancer Research
Daniel Nava Rodrigues: The Institute of Cancer Research
Katherine Eason: The Institute of Cancer Research
Anguraj Sadanandam: The Institute of Cancer Research
Cecilia Orbegoso: The Royal Marsden NHS Foundation Trust
Marco Punta: The Institute of Cancer Research
Andrea Sottoriva: The Institute of Cancer Research
Stefano Lise: The Institute of Cancer Research
Susana Banerjee: The Royal Marsden NHS Foundation Trust
Yinyin Yuan: The Institute of Cancer Research

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06130-3

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