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Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns.
(NATURE PORTFOLIO, 2021-08-01)
Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at ...
A Big Bang model of human colorectal tumor growth.
(NATURE PUBLISHING GROUP, 2015-03-01)
What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion ...
Resolving genetic heterogeneity in cancer.
(NATURE PUBLISHING GROUP, 2019-07-01)
To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and ...
Measuring single cell divisions in human tissues from multi-region sequencing data.
(NATURE PUBLISHING GROUP, 2020-02-25)
Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in ...
Quantification of subclonal selection in cancer from bulk sequencing data.
(NATURE PUBLISHING GROUP, 2018-05-28)
Subclonal architectures are prevalent across cancer types. However, the temporal evolutionary dynamics that produce tumor subclones remain unknown. Here we measure clone dynamics in human cancers by using computational ...
Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-08-05)
Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to ...
The MOBSTER R package for tumour subclonal deconvolution from bulk DNA whole-genome sequencing data.
(BMC, 2020-11-17)
BACKGROUND: The large-scale availability of whole-genome sequencing profiles from bulk DNA sequencing of cancer tissues is fueling the application of evolutionary theory to cancer. From a bulk biopsy, subclonal deconvolution ...
Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data.
(PUBLIC LIBRARY SCIENCE, 2019-07-29)
Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth ...
Measuring Clonal Evolution in Cancer with Genomics.
(ANNUAL REVIEWS, 2019-08-31)
Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal ...
Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
(ELIFE SCIENCES PUBLICATIONS LTD, 2020-03-30)
The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in ...