Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genetic Diversity in Circulating Tumor Cell Clusters

Zafarali Ahmed, Simon Gravel
doi: https://doi.org/10.1101/113480
Zafarali Ahmed
1Department of Biology, McGill University, Montreal, Quebec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon Gravel
2Department of Human Genetics, McGill University, Montreal, Quebec, Canada
3McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Genetic diversity plays a central role in tumor progression, metastasis, and resistance to treatment. Experiments are shedding light on this diversity at ever finer scales, but interpretation is challenging. Using recent progress in numerical models, we simulate macroscopic tumors to investigate the interplay between global growth dynamics, microscopic composition, and circulating tumor cell cluster diversity. We find that modest differences in growth parameters can profoundly change microscopic diversity. Simple outwards expansion leads to spatially segregated clones, as expected, but a modest cell turnover can result in mixing at the microscopic scale, consistent with experimental observations. Whereas simple range expansion models predict maximum diversity at the tumor edge, turnover models predict maximum diversity near the core of the tumor and a higher potency of CTCs for metastasis. Using multi-region sequencing data from a Hepatocellular Carcinoma patient to validate our models, we propose that deep multi-region sequencing is well-powered to distinguish between some of the leading models of cancer evolution. The genetic composition of circulating tumor cell clusters, which can be obtained from noninvasive blood draws, is therefore informative about tumor evolution, the position of origin of the cluster within the tumor, and its metastatic potential. It is therefore a promising tool for both fundamental and medical research.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted March 03, 2017.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genetic Diversity in Circulating Tumor Cell Clusters
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genetic Diversity in Circulating Tumor Cell Clusters
Zafarali Ahmed, Simon Gravel
bioRxiv 113480; doi: https://doi.org/10.1101/113480
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Genetic Diversity in Circulating Tumor Cell Clusters
Zafarali Ahmed, Simon Gravel
bioRxiv 113480; doi: https://doi.org/10.1101/113480

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4382)
  • Biochemistry (9591)
  • Bioengineering (7090)
  • Bioinformatics (24856)
  • Biophysics (12600)
  • Cancer Biology (9956)
  • Cell Biology (14349)
  • Clinical Trials (138)
  • Developmental Biology (7948)
  • Ecology (12105)
  • Epidemiology (2067)
  • Evolutionary Biology (15988)
  • Genetics (10925)
  • Genomics (14738)
  • Immunology (9869)
  • Microbiology (23659)
  • Molecular Biology (9484)
  • Neuroscience (50856)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2681)
  • Physiology (4013)
  • Plant Biology (8657)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2394)
  • Systems Biology (6433)
  • Zoology (1346)