ArticleMolecular cancer research : MCR2019
Mitochondrial DNA Mutations are Associated with Ulcerative Colitis Preneoplasia but Tend to be Negatively Selected in Cancer.
Article in Molecular cancer research : MCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Mitochondrial Dysfunction in Ulcerative Colitis: Pathogenic Mechanisms and Novel Therapeutics.Journal of biochemical and molecular toxicology · 2026Review
- Mitochondrial DNA Mutations in Colorectal Cancer Stem Cells: Implications for Tumor Dynamics and Therapeutic Strategies.Current medicinal chemistry · 2026Review
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- A Comprehensive Review of the Contribution of Mitochondrial DNA Mutations and Dysfunction in Polycystic Ovary Syndrome, Supported by Secondary Database Analysis.International journal of molecular sciences · 2025Review
- Variable heteroplasmy of the Common 9-bp Deletion in the Human Mitochondrial Genome in Ancient and Present-Day Populations.microPublication biology · 2025Article
- Mitochondrial function and gastrointestinal diseases.Nature reviews. Gastroenterology & hepatology · 2024Review
- Autophagy in Disease Onset and Progression.Aging and disease · 2024Review
- The role of mitochondrial DNA copy number in autoimmune disease: a bidirectional two sample mendelian randomization study.Frontiers in immunology · 2024Article
- Changes in metabolic landscapes shape divergent but distinct mutational signatures and cytotoxic consequences of redox stress.Nucleic acids research · 2023Article
- Article
- Mutation accumulation in mtDNA of cancers resembles mutagenesis in normal stem cells.iScience · 2022Article
- A mitochondria-specific mutational signature of aging: increased rate of A > G substitutions on the heavy strand.Nucleic acids research · 2022Article
- Mutational profiling of mtDNA control region reveals tumor-specific evolutionary selection involved in mitochondrial dysfunction.EBioMedicine · 2022Article
- The Complicated Nature of Somatic mtDNA Mutations in Aging.Frontiers in aging · 2022Article
- Analyzing the metabolic fate of oral administration drugs: A review and state-of-the-art roadmap.Frontiers in pharmacology · 2022Review
- A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA.Nucleic acids research · 2021Article
- The Role of Mitochondria Dysfunction in Inflammatory Bowel Diseases and Colorectal Cancer.International journal of molecular sciences · 2021Review
- OMA1 reprograms metabolism under hypoxia to promote colorectal cancer development.EMBO reports · 2021Article
- Increased levels of 5',8-Cyclopurine DNA lesions in inflammatory bowel diseases.Redox biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The role of mitochondrial DNA (mtDNA) mutations in cancer remains controversial. Ulcerative colitis is an inflammatory bowel disease that increases the risk of colorectal cancer and involves mitochondrial dysfunction, making it an ideal model to study the role of mtDNA in tumorigenesis. Our goal was to comprehensively characterize mtDNA mutations in ulcerative colitis tumorigenesis using Duplex Sequencing, an ultra-accurate next-generation sequencing method. We analyzed 46 colon biopsies from non-ulcerative colitis control patients and ulcerative colitis patients with and without cancer, including biopsies at all stages of dysplastic progression. mtDNA was sequenced at a median depth of 1,364x. Mutations were classified by mutant allele frequency: clonal > 0.95, subclonal 0.01-0.95, and very low frequency (VLF) < 0.01. We identified 208 clonal and subclonal mutations and 56,764 VLF mutations. Mutations were randomly distributed across the mitochondrial genome. Clonal and subclonal mutations increased in number and pathogenicity in early dysplasia, but decreased in number and pathogenicity in cancer. Most clonal, subclonal, and VLF mutations were C>T transitions in the heavy strand of mtDNA, which likely arise from DNA replication errors. A subset of VLF mutations were C>A transversions, which are probably due to oxidative damage. VLF transitions and indels were less abundant in the non-D-loop region and decreased with progression. Our results indicate that mtDNA mutations are frequent in ulcerative colitis preneoplasia but negatively selected in cancers. IMPLICATIONS: While mtDNA mutations might contribute to early ulcerative colitis tumorigenesis, they appear to be selected against in cancer, suggesting that functional mitochondria might be required for malignant transformation in ulcerative colitis.
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Registered trials
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