Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity

Nature Communications
Andreas HeindlYinyin 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.

References

Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Apr 15, 2003·Nature Medicine·Toshiyasu TaniguchiAlan D D'Andrea
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
May 3, 2006·The American Journal of Pathology·Mariana Rodríguez ZubietaJosé Mordoh
Jun 15, 2006·Journal of Cell Science·Kaliyaperumal ManjuVeena K Parnaik
Jul 11, 2008·BMC Bioinformatics·Korbinian Strimmer
Aug 14, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard W TothillDavid D L Bowtell
Aug 21, 2008·PloS One·Naomi D WillisChristopher J Hutchison
Jan 23, 2009·Molecular Biology of the Cell·Douglas R MackayKatharine S Ullman
Jan 24, 2009·Nature Reviews. Cancer·Darci T ButcherValerie M Weaver
Feb 3, 2009·Behavior Research Methods·Frank KellerMartin Corley
Jul 8, 2009·Molecular and Cellular Biology·Callinice D Capo-chichiXiang-Xi Xu
May 14, 2010·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Leonard Da Silva, Sunil R Lakhani
May 26, 2010·Molecular Cancer·Chieko HashizumeRichard W Wong
Nov 27, 2010·Current Opinion in Cell Biology·Peter FriedlJan Lammerding
Feb 4, 2011·Molecular Biology of the Cell·Yvonne C LussiBirthe Fahrenkrog
Jun 28, 2011·Cell Cycle·Abena B RedwoodSusana Gonzalo
Jun 30, 2011·The EMBO Journal·Shigeru TsuboiChikara Ohyama
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Dec 24, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Robert A SoslowDouglas A Levine
Jan 20, 2012·Nature·Mel Greaves, Carlo C Maley
Feb 18, 2012·Nature Reviews. Cancer·Kin-Hoe ChowKatharine S Ullman
Jun 15, 2012·Nature Reviews. Cancer·Robert J GilliesRobert A Gatenby
Oct 27, 2012·Science Translational Medicine·Yinyin YuanFlorian Markowetz
Jan 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Susana Banerjee, Stanley B Kaye
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Mar 19, 2013·Cell·Katherine H Schreiber, Brian K Kennedy
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Sep 21, 2013·Nature·Melissa R Junttila, Frederic J de Sauvage
Oct 12, 2013·Nature Communications·Kosuke YoshiharaRoel G W Verhaak
Jan 8, 2014·BMC Systems Biology·Gundián M de Hijas-ListeJulio R Banga
May 23, 2014·IEEE Transactions on Bio-medical Engineering·Adnan Mujahid KhanDerek Magee
Jun 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael D IglesiaJonathan S Serody
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Mar 31, 2015·Nature Methods·Aaron M NewmanAsh A Alizadeh
Jun 21, 2015·Cancer Discovery·Charles SwantonReuben S Harris

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Citations

Jun 9, 2020·Expert Review of Molecular Diagnostics·Arman RahmanWilliam M Gallagher
May 29, 2020·Nature Medicine·Khalid AbdulJabbarYinyin Yuan
May 7, 2019·Annual Review of Genomics and Human Genetics·Marc J WilliamsTrevor A Graham
Dec 12, 2019·F1000Research·Oscar MaiquesVictoria Sanz-Moreno
Aug 14, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stephanie LheureuxRobert Coleman
Aug 14, 2019·Ultrasound in Medicine & Biology·Lifen XieQuanhong Liu
Mar 3, 2021·Nature Biomedical Engineering·Ming Y LuFaisal Mahmood

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Methods Mentioned

BETA
SMA
surgical resection
dissect
exome sequencing

Software Mentioned

limma
R
platypus
MuTect2
ABSOLUTE
CIBERSORT
Bioconductor
bfconvert
R package CRImage
R package HTSanalyzeR

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