ArticlePLoS computational biology2019
Estimating the number of genetic mutations (hits) required for carcinogenesis based on the distribution of somatic mutations.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 78 citations in OpenAlex.
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- Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning.Nature communications · 2025Article
- Telomere function and regulation from mouse models to human ageing and disease.Nature reviews. Molecular cell biology · 2025Review
- Characterization of cancer-driving nucleotides (CDNs) across genes, cancer types, and patients.eLife · 2024Article
- The theory of massively repeated evolution and full identifications of cancer-driving nucleotides (CDNs).eLife · 2024Article
- Single cell spatial biology over developmental time can decipher pediatric brain pathologies.Neurobiology of disease · 2024Review
- Mitogen signaling strength and duration can control cell cycle decisions.Science advances · 2024Review
- Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data.Blood cancer journal · 2024Article
- Personalized Driver Gene Prediction Using Graph Convolutional Networks with Conditional Random Fields.Biology · 2024Article
- The Risk Function of Breast and Ovarian Cancers in the Avrami-Dobrzyński Cellular Phase-Transition Model.International journal of molecular sciences · 2024Article
- Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly AvailableEnvironmental health perspectives · 2024Article
- Potential immunosuppressive clonal hematopoietic mutations in tumor infiltrating immune cells in breast invasive carcinoma.Scientific reports · 2023Article
- The Cell Transformation Assay: A Historical Assessment of Current Knowledge of Applications in an Integrated Approach to Testing and Assessment for Non-Genotoxic Carcinogens.International journal of molecular sciences · 2023Review
- Mutation-derived, genomic instability-associated lncRNAs are prognostic markers in gliomas.PeerJ · 2023Article
- Next-generation sequencing and molecular therapy.Clinical medicine (London, England) · 2023Article
- Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles.Frontiers in oncology · 2023Article
- A computational model for the cancer field effect.Frontiers in artificial intelligence · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Individual instances of cancer are primarily a result of a combination of a small number of genetic mutations (hits). Knowing the number of such mutations is a prerequisite for identifying specific combinations of carcinogenic mutations and understanding the etiology of cancer. We present a mathematical model for estimating the number of hits based on the distribution of somatic mutations. The model is fundamentally different from previous approaches, which are based on cancer incidence by age. Our somatic mutation based model is likely to be more robust than age-based models since it does not require knowing or accounting for the highly variable mutation rate, which can vary by over three orders of magnitude. In fact, we find that the number of somatic mutations at diagnosis is weakly correlated with age at cancer diagnosis, most likely due to the extreme variability in mutation rates between individuals. Comparing the distribution of somatic mutations predicted by our model to the actual distribution from 6904 tumor samples we estimate the number of hits required for carcinogenesis for 17 cancer types. We find that different cancer types exhibit distinct somatic mutational profiles corresponding to different numbers of hits. Why might different cancer types require different numbers of hits for carcinogenesis? The answer may provide insight into the unique etiology of different cancer types.
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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.