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Exploring Ductal Carcinoma In-Situ to Invasive Ductal Carcinoma Transitions Using Energy Minimization Principles

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Computational Science – ICCS 2022 (ICCS 2022)

Part of the book series: Lecture Notes in Computer Science ((LNCS,volume 13350))

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Abstract

Ductal carcinoma in-situ (DCIS) presents a risk of transformation to malignant intraductal carcinoma (IDC) of the breast. Three tumor suppressor genes RB, BRCA1 and TP53 are critical in curtailing the progress of DCIS to IDC. The complex transition process from DCIS to IDC involves acquisition of intracellular genomic aberrations and consequent changes in phenotypic characteristics and protein expression level of the cells. The spatiotemporal dynamics associated with breech of epithelial basement membrane and subsequent invasion of stromal tissues during the transition is less understood. We explore the emergence of invasive behavior in benign tumors, emanating from altered expression levels of the three critical genes. A multiscale mechanistic model based on Glazier-Graner-Hogeweg method-based modelling (GGH) is used to unravel the phenotypical and biophysical dynamics promoting the invasive nature of DCIS. Ductal morphologies including comedo, hyperplasia and DCIS, evolve spontaneously from the interplay between the gene activity parameters in the simulations. The spatiotemporal model elucidates the cause-and-effect relationship between cell-level biological signaling and tissue-level biophysical response in the ductal microenvironment. The model predicts that BRCA1 mutations will act as a facilitator for DCIS to IDC transitions while mutations in RB act as initiator of such transitions.

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Authors and Affiliations

  1. HEALTHTECH NTU, Interdisciplinary Graduate School, Nanyang Technological University, Singapore, Singapore

    Vivek M. Sheraton

  2. Institute for Advanced Study, University of Amsterdam, Amsterdam, The Netherlands

    Vivek M. Sheraton

  3. Center for Experimental and Molecular Medicine, UMC Location University of Amsterdam, Amsterdam, The Netherlands

    Vivek M. Sheraton

  4. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore

    Shijun Ma

Authors
  1. Vivek M. Sheraton
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  2. Shijun Ma
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Correspondence to Vivek M. Sheraton .

Editor information

Editors and Affiliations

  1. Brunel University London, London, UK

    Derek Groen

  2. University of Amsterdam, Amsterdam, The Netherlands

    Clélia de Mulatier

  3. AGH University of Science and Technology, Krakow, Poland

    Maciej Paszynski

  4. University of Amsterdam, Amsterdam, The Netherlands

    Valeria V. Krzhizhanovskaya

  5. University of Tennessee at Knoxville, Knoxville, TN, USA

    Jack J. Dongarra

  6. University of Amsterdam, Amsterdam, The Netherlands

    Peter M. A. Sloot

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Sheraton, V.M., Ma, S. (2022). Exploring Ductal Carcinoma In-Situ to Invasive Ductal Carcinoma Transitions Using Energy Minimization Principles. In: Groen, D., de Mulatier, C., Paszynski, M., Krzhizhanovskaya, V.V., Dongarra, J.J., Sloot, P.M.A. (eds) Computational Science – ICCS 2022. ICCS 2022. Lecture Notes in Computer Science, vol 13350. Springer, Cham. https://doi.org/10.1007/978-3-031-08751-6_27

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  • DOI: https://doi.org/10.1007/978-3-031-08751-6_27

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-08750-9

  • Online ISBN: 978-3-031-08751-6

  • eBook Packages: Computer ScienceComputer Science (R0)

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