Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Andreas Heindl, Adnan Mujahid Khan, Daniel Nava Rodrigues, Katherine Eason, Anguraj Sadanandam, Cecilia Orbegoso, Marco Punta, Andrea Sottoriva, Stefano Lise, Susana Banerjee, Yinyin Yuan

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. More... »

PAGES

3917

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-06130-3

DOI

http://dx.doi.org/10.1038/s41467-018-06130-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107107969

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30254278


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