ArticleGenome biology2019
An enhanced genetic model of colorectal cancer progression history.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 49 citations in OpenAlex.
- Advancing risk gene discovery across the allele frequency spectrum.HGG advances · 2026Review
- Fulminant development of a giant pelvic metastasis from microsatellite-stable early-onset sigmoid colon cancer with KRAS and TP53 co-mutations: a case report.Frontiers in medicine · 2026Article
- Article
- High-resolution detection of copy number alterations in single cells with HiScanner.Nature communications · 2025Article
- High-resolution detection of copy number alterations in single cells with HiScanner.bioRxiv : the preprint server for biology · 2025Article
- Exploration of Blood Metabolite Signatures of Colorectal Cancer and Polyposis through Integrated Statistical and Network Analysis.Metabolites · 2023Article
- Recent advances in nanomedicine preparative methods and their therapeutic potential for colorectal cancer: a critical review.Frontiers in oncology · 2023Review
- Immune function of colon cancer associated miRNA and target genes.Frontiers in immunology · 2023Article
- Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles.Frontiers in oncology · 2023Article
- Starfish infers signatures of complex genomic rearrangements across human cancers.Nature cancer · 2022Article
- Comprehensive characterization of clonality of driver genes revealing their clinical relevance in colorectal cancer.Journal of translational medicine · 2022Article
- Computational analysis of cancer genome sequencing data.Nature reviews. Genetics · 2022Review
- Clustered 8-Oxo-Guanine Mutations and Oncogenic Gene Fusions in Microsatellite-Unstable Colorectal Cancer.JCO precision oncology · 2022Article
- Comparison of the copy-neutral loss of heterozygosity identified from whole-exome sequencing data using three different tools.Genomics & informatics · 2022Article
- Oral-Intestinal Microbiota in Colorectal Cancer: Inflammation and Immunosuppression.Journal of inflammation research · 2022Review
- Roburic Acid Targets TNF to Inhibit the NF-κB Signaling Pathway and Suppress Human Colorectal Cancer Cell Growth.Frontiers in immunology · 2022Article
- miR-1266-3p Suppresses Epithelial-Mesenchymal Transition in Colon Cancer by Targeting P4HA3.Analytical cellular pathology (Amsterdam) · 2022Article
- Fecal metabolomic profiles: A comparative study of patients with colorectal cancerWorld journal of gastroenterology · 2021Article
- Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage.Cell communication and signaling : CCS · 2021Review
- Elements and evolutionary determinants of genomic divergence between paired primary and metastatic tumors.PLoS computational biology · 2021Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe classical genetic model of colorectal cancer presents APC mutations as the earliest genomic alterations, followed by KRAS and TP53 mutations. However, the timing and relative order of clonal expansion and other types of genomic alterations, such as genomic rearrangements, are still unclear.
resultsHere, we perform comprehensive bioinformatic analysis to dissect the relative timing of somatic genetic alterations in 63 colorectal cancers with whole-genome sequencing data. Utilizing allele fractions of somatic single nucleotide variants as molecular clocks while accounting for the presence of copy number changes and structural alterations, we identify key events in the evolution of colorectal tumors. We find that driver point mutations, gene fusions, and arm-level copy losses typically arise early in tumorigenesis; different mechanisms act on distinct genomic regions to drive DNA copy changes; and chromothripsis-clustered rearrangements previously thought to occur as a single catastrophic event-is frequent and may occur multiple times independently in the same tumor through different mechanisms. Furthermore, our computational approach reveals that, in contrast to recent studies, selection is often present on subclones and that multiple evolutionary models can operate in a single tumor at different stages.
conclusionCombining these results, we present a refined tumor progression model which significantly expands our understanding of the tumorigenic process of human colorectal cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.