ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hypermutable DNA chronicles the evolution of human colon cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Multiregion ultra-deep sequencing reveals early intermixing and variable levels of intratumoral heterogeneity in colorectal cancer.Molecular oncology · 2017Trial
- Inclusion of tumor periphery in radiomics analysis of magnetic resonance images does not improve predictions of preoperative therapy response in patients with rectal cancer.Abdominal radiology (New York) · 2026Article
- A single-cell derived spheroid approach to dissect intratumoural heterogeneity in colorectal cancer: cell lines show changes in proteomes and therapeutic response to 5-FU.Journal of cancer research and clinical oncology · 2026Article
- Evolutionary paths towards metastasis.Nature reviews. Cancer · 2025Review
- Quantifying cell divisions along evolutionary lineages in cancer.Nature genetics · 2025Article
- Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors.Nature cancer · 2024Article
- A unique interplay of access and selection shapes peritoneal metastasis evolution in colorectal cancer.bioRxiv : the preprint server for biology · 2024Article
- Inferring parameters of cancer evolution in chronic lymphocytic leukemia.PLoS computational biology · 2022Article
- The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment.Frontiers in pharmacology · 2022Review
- PolyG-DS: An ultrasensitive polyguanine tract-profiling method to detect clonal expansions and trace cell lineage.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics.Nature reviews. Genetics · 2021Review
- Intratumor heterogeneity: A new perspective on colorectal cancer research.Cancer medicine · 2020Review
- Mapping the spreading routes of lymphatic metastases in human colorectal cancer.Nature communications · 2020Article
- Cancer recurrence times from a branching process model.PLoS computational biology · 2019Article
- Unstable Genome and Transcriptome Dynamics during Tumor Metastasis Contribute to Therapeutic Heterogeneity in Colorectal Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations.Nature reviews. Genetics · 2018Review
- The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome.BMC medicine · 2017Review
- Origins of lymphatic and distant metastases in human colorectal cancer.Science (New York, N.Y.) · 2017Article
- The evolution of tumour phylogenetics: principles and practice.Nature reviews. Genetics · 2017Review
- CRISPR-Cas9-targeted fragmentation and selective sequencing enable massively parallel microsatellite analysis.Nature communications · 2017Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumor genetic heterogeneity reflects the evolutionary history of a cancer and is thought to influence treatment outcomes. Here we report that a simple PCR-based assay interrogating somatic variation in hypermutable polyguanine (poly-G) repeats can provide a rapid and reliable assessment of mitotic history and clonal architecture in human cancer. We use poly-G repeat genotyping to study the evolution of colon carcinoma. In a cohort of 22 patients, we detect poly-G variants in 91% of tumors. Patient age is positively correlated with somatic mutation frequency, suggesting that some poly-G variants accumulate before the onset of carcinogenesis during normal division in colonic stem cells. Poorly differentiated tumors have fewer mutations than well-differentiated tumors, possibly indicating a shorter mitotic history of the founder cell in these cancers. We generate poly-G mutation profiles of spatially separated samples from primary carcinomas and matched metastases to build well-supported phylogenetic trees that illuminate individual patients' path of metastatic progression. Our results show varying degrees of intratumor heterogeneity among patients. Finally, we show that poly-G mutations can be found in other cancers than colon carcinoma. Our approach can generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.
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Registered trials
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.