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Phylogenetic Quantification of Intra-tumour Heterogeneity

Roland F. Schwarz, Anne Trinh, Botond Sipos, James D. Brenton, Nick Goldman, Florian Markowetz, Niko Beerenwinkel
2014 PLoS Computational Biology  
Intra-tumour heterogeneity (ITH) is the result of ongoing evolutionary change within each cancer.  ...  Results: To address these challenges we present MEDICC, a method for phylogenetic reconstruction and ITH quantification based on a Minimum Event Distance for Intra-tumour Copynumber Comparisons.  ...  Evolutionary comparisons with MEDICC allow quantification of tumour heterogeneity Intra-tumour heterogeneity is a loose concept that describes the amount of genomic difference between multiple cells or  ... 
doi:10.1371/journal.pcbi.1003535 pmid:24743184 pmcid:PMC3990475 fatcat:rahgrc6fizdtpjjznb22763y4e

Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis

Roland F. Schwarz, Charlotte K. Y. Ng, Susanna L. Cooke, Scott Newman, Jillian Temple, Anna M. Piskorz, Davina Gale, Karen Sayal, Muhammed Murtaza, Peter J. Baldwin, Nitzan Rosenfeld, Helena M. Earl (+6 others)
2015 PLoS Medicine  
The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the  ...  Methods and Findings Evolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide  ...  (A) Numerical quantification of intra-tumour genetic heterogeneity by evolutionary comparisons.Copy number profiles from 135 metastatic sites were obtained for 17 patients with HGSOC.  ... 
doi:10.1371/journal.pmed.1001789 pmid:25710373 pmcid:PMC4339382 fatcat:xvsgmzgxznfnfbrkfkgjdfuwca

Tumour Cell Heterogeneity

Laura Gay, Ann-Marie Baker, Trevor A. Graham
2016 F1000Research  
Khalique L, Ayhan A, Weale ME, et al.: Genetic intra-tumour heterogeneity in epithelial ovarian cancer and its implications for molecular diagnosis of tumours. J Pathol. 2007; 211(3): 286-95.  ...  In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the  ...  The origins of intra-tumour heterogeneity Intra-tumour heterogeneity (ITH) has been documented for many decades, initially from a morphological perspective 1,2 .  ... 
doi:10.12688/f1000research.7210.1 pmid:26973786 pmcid:PMC4776671 fatcat:3mf7vhvixreptmblsbvf3gr5zq

Quantification of tumour evolution and heterogeneity via Bayesian epiallele detection [article]

James E. Barrett, Andrew Feber, Javier Herrero, Miljana Tanic, Gareth Wilson, Charles Swanton, Stephan Beck
2017 arXiv   pre-print
Motivation: Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment.  ...  By tracing the distribution of epialleles throughout the tumour we can infer the phylogenetic history of the tumour, identify epialleles that differ between normal and cancer tissue, and define a measure  ...  Analysing multiple tissue samples from different tumour regions facilitates quantification of tumour heterogeneity and phylogenetic analyses.  ... 
arXiv:1702.00633v2 fatcat:axdvhumdi5fcxl5gjlzo7tzuoq

Quantification of tumour evolution and heterogeneity via Bayesian epiallele detection

James E. Barrett, Andrew Feber, Javier Herrero, Miljana Tanic, Gareth A. Wilson, Charles Swanton, Stephan Beck
2017 BMC Bioinformatics  
Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment.  ...  By tracing the distribution of epialleles throughout the tumour we can infer the phylogenetic history of the tumour, identify epialleles that differ between normal and cancer tissue, and define a measure  ...  Analysing multiple tissue samples from different tumour regions facilitates quantification of tumour heterogeneity and phylogenetic analyses.  ... 
doi:10.1186/s12859-017-1753-2 pmid:28743252 pmcid:PMC5526259 fatcat:e5r2homxpbc2roepc3gdnvzxpq

OncoPhase: Quantification of somatic mutation cellular prevalence using phase information [article]

Donatien Chedom-Fotso, Ahmed Ashour Ahmed, Christopher Yau
2016 bioRxiv   pre-print
Genome sequencing allows us to identify mutations but the prevalence of those mutations in heterogeneous tumours must be inferred.  ...  We describe a method that we call OncoPhase to compute the prevalence of somatic point mutations from genome sequencing analysis of heterogeneous tumours that combines information from nearby phased germline  ...  Introduction Cancer exhibits extensive intra-tumour heterogeneity with multiple sub-populations of tumour cells containing both common and private somatic mutations.  ... 
doi:10.1101/046631 fatcat:pduil56k3bevbah3lkwrvuffwm

The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer

Peter Barry, Alexandra Vatsiou, Inmaculada Spiteri, Daniel Nichol, George D. Cresswell, Ahmet Acar, Nicholas Trahearn, Sarah Hrebien, Isaac Garcia-Murillas, Kate Chkhaidze, Luca Ermini, Ian Said Huntingford (+13 others)
2018 Clinical Cancer Research  
demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.  ...  Divergence of metastatic subclones was driven in part by APOBEC.  ...  Extensive intra-tumour heterogeneity (ITH) was evident our cohort, with an average of 73.5% of variants considered to be subclonal (Fig. S1 and S2 ).  ... 
doi:10.1158/1078-0432.ccr-17-3374 pmid:29891724 pmcid:PMC6296441 fatcat:36g6xvwog5bgrc56chx53u7diu

Single cell analysis of cancer genomes

Peter Van Loo, Thierry Voet
2014 Current Opinion in Genetics and Development  
(b) To study tumour evolution and intra-tumour genetic heterogeneity, individual tumour cells can be isolated using a variety of techniques.  ...  It allows characterization of intra-tumour genetic heterogeneity genome-wide to single-cell resolution, and thereby offers a unique viewpoint into tumour evolution.  ... 
doi:10.1016/j.gde.2013.12.004 pmid:24531336 fatcat:iepaolljkrhkhmnldv6pmdx3vm

Longitudinal Monitoring of Intra-Tumoural Heterogeneity Using Optical Barcoding of Patient-Derived Colorectal Tumour Models

Carolyn Shembrey, Jai Smith, Mélodie Grandin, Nathalia Williams, Hyun-Jung Cho, Christina Mølck, Corina Behrenbruch, Benjamin NJ. Thomson, Alexander G. Heriot, Delphine Merino, Frédéric Hollande
2022 Cancers  
However, due to the technical difficulty associated with studying such intra-tumoural heterogeneity, this phenomenon is seldom interrogated in conventional cell culture models.  ...  Geno- and phenotypic heterogeneity amongst cancer cell subpopulations are established drivers of treatment resistance and tumour recurrence.  ...  & Microscopy (PMCC) and Biological Optical Microscopy Platform (University of Melbourne).  ... 
doi:10.3390/cancers14030581 pmid:35158849 pmcid:PMC8833441 fatcat:6iow6wt4vbfu3jrvokr3wy7qqy

Clonal Evolution and Timing of Metastatic Colorectal Cancer

Sarah Siraj, Tariq Masoodi, Abdul K. Siraj, Saud Azam, Zeeshan Qadri, Saeeda O. Ahmed, Wafaa N. AlBalawy, Khadija A. Al-Obaisi, Sandeep K. Parvathareddy, Hadeel M. AlManea, Hussah F. AlHussaini, Alaa Abduljabbar (+4 others)
2020 Cancers  
Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours (n = 92 tumour regions) and metastases (n = 99 tumour regions  ...  intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.  ...  Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/cancers12102938 pmid:33053768 fatcat:tsbygyglezekjhku5zedl4hc4u

Evaluating statistical approaches to define clonal origin of tumours using bulk DNA sequencing: context is everything

Tanjina Kader, Magnus Zethoven, Kylie L. Gorringe
2022 Genome Biology  
AbstractClonal analysis of tumour sequencing data enables the evaluation of the relationship of histologically distinct synchronous lesions, such as co-existing benign areas, and temporally distinct tumours  ...  In this review, we summarise statistical approaches that are commonly employed to define tumour clonal relatedness using data from bulk DNA technologies.  ...  Without unravelling the intra-tumoural spatial heterogeneity, we might not be able to determine the evolutionary bottleneck of DCIS progressing to IDC.  ... 
doi:10.1186/s13059-022-02600-6 pmid:35109903 pmcid:PMC8809045 fatcat:uj6saf43ifezjpjhn6mtp5pw2y

Personalised mapping of tumour development in synchronous colorectal cancer patients

Valentina Thomas, Maura B. Cotter, Miriam Tosetto, Yi Ling Khaw, Robert Geraghty, Desmond C. Winter, Elizabeth J. Ryan, Kieran Sheahan, Simon J. Furney
2020 npj Genomic Medicine  
Microbial analysis revealed the presence of Fusobacterium nucleatum species in patients with MSI tumours, while quantification of tumour immune infiltration showed varying immune responses between syCRCs  ...  Overlap of mutations between synchronous tumours was consistently low (<0.5%) and heterogeneity of driver events across syCRCs was high in all patients.  ...  The main challenge in the treatment of this disease is its high intra-and inter-tumour heterogeneity, which develops through multiple genetic and epigenetic pathways of genome instability, each contributing  ... 
doi:10.1038/s41525-020-0134-3 pmid:32655884 pmcid:PMC7335056 fatcat:owo2a6ufqjelljl7ycpbgan3ly

Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Roy Rabbie, Naser Ansari-Pour, Oliver Cast, Doreen Lau, Francis Scott, Sarah J. Welsh, Christine Parkinson, Leila Khoja, Luiza Moore, Mark Tullett, Kim Wong, Ingrid Ferreira (+11 others)
2020 Nature Communications  
Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations  ...  of inferring heterogeneity from a single biopsy.  ...  The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.  ... 
doi:10.1038/s41467-020-18060-0 pmid:32855398 pmcid:PMC7453196 fatcat:nu3rxrvrrzetpgvsoizqncq6zq

Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling

Ali Bashashati, Gavin Ha, Alicia Tone, Jiarui Ding, Leah M Prentice, Andrew Roth, Jamie Rosner, Karey Shumansky, Steve Kalloger, Janine Senz, Winnie Yang, Melissa McConechy (+13 others)
2013 Journal of Pathology  
We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy.  ...  We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including  ...  (D) Phylogenetic tree of discrete compound events.  ... 
doi:10.1002/path.4230 pmid:23780408 pmcid:PMC3864404 fatcat:f6tmd3vyuffvlb37d6wdv3b72e

Comprehensive analysis of tumour initiation, spatial and temporal progression under multiple lines of treatment [article]

Ignaty Leshchiner, Dimitri Livitz, Justin F. Gainor, Daniel Rosebrock, Oliver Spiro, Aina Martinez, Edmund Mroz, Jessica J. Lin, Chip Stewart, Jaegil Kim, Liudmila Elagina, Ivana Bozic (+8 others)
2018 bioRxiv   pre-print
This methodology will enable a systematic study of tumour initiation, progression and resistance across cancer types and therapies.  ...  PhylogicNDT can be used to infer: (i) the order of clonal driver events (including in pre-cancerous stages); (ii) subclonal populations of cells and their phylogenetic relationships; and (iii) cell population  ...  This intra-sample heterogeneity is even more pronounced in cases when different sampling techniques are used for collecting tumour material, e.g., slices from large tumour resections, core needle biopsy  ... 
doi:10.1101/508127 fatcat:66fd7emnebbytgftzh3yeatmb4
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