ArticlePloS one2013
Fhit deficiency-induced global genome instability promotes mutation and clonal expansion.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Single-cell and Mendelian analyses reveal shared mechanisms between head and neck neoplasms and aging.Discover oncology · 2026Article
- Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.Experimental & molecular medicine · 2025Article
- Integrated analysis ofCell cycle (Georgetown, Tex.) · 2024Review
- Review
- Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases.International review of cell and molecular biology · 2018Review
- The ubiquitous 'cancer mutational signature' 5 occurs specifically in cancers with deletedOncotarget · 2017Article
- Wwox-Brca1 interaction: role in DNA repair pathway choice.Oncogene · 2017Article
- Identification of Fhit as a post-transcriptional effector of Thymidine Kinase 1 expression.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Article
- Fhit and Wwox loss-associated genome instability: A genome caretaker one-two punch.Advances in biological regulation · 2017Article
- Fhit loss-associated initiation and progression of neoplasia in vitro.Cancer science · 2016Article
- Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation.Cancer medicine · 2016Article
- Exome-wide single-base substitutions in tissues and derived cell lines of the constitutive Fhit knockout mouse.Cancer science · 2016Article
- WWOX: a fragile tumor suppressor.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- FHIT loss-induced DNA damage creates optimal APOBEC substrates: Insights into APOBEC-mediated mutagenesis.Oncotarget · 2015Article
- Very large common fragile site genes and their potential role in cancer development.Cellular and molecular life sciences : CMLS · 2014Review
- The FHIT gene product: tumor suppressor and genome "caretaker".Cellular and molecular life sciences : CMLS · 2014Review
- The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability.Cellular and molecular life sciences : CMLS · 2014Review
- WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis.Cancers · 2014Article
- A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Loss of Fhit expression, encoded at chromosome fragile site FRA3B, leads to increased replication stress, genome instability and accumulation of genetic alterations. We have proposed that Fhit is a genome 'caretaker' whose loss initiates genome instability in preneoplastic lesions. We have characterized allele copy number alterations and expression changes observed in Fhit-deficient cells in conjunction with alterations in cellular proliferation and exome mutations, using cells from mouse embryo fibroblasts (MEFs), mouse kidney, early and late after establishment in culture, and in response to carcinogen treatment. Fhit (-/-) MEFs escape senescence to become immortal more rapidly than Fhit (+/+) MEFs; -/- MEFs and kidney cultures show allele losses and gains, while +/+ derived cells show few genomic alterations. Striking alterations in expression of p53, p21, Mcl1 and active caspase 3 occurred in mouse kidney -/- cells during progressive tissue culture passage. To define genomic changes associated with preneoplastic changes in vivo, exome DNAs were sequenced for +/+ and -/- liver tissue after treatment of mice with the carcinogen, 7,12-dimethylbenz[a]anthracene, and for +/+ and -/- kidney cells treated in vitro with this carcinogen. The -/- exome DNAs, in comparison with +/+ DNA, showed small insertions, deletions and point mutations in more genes, some likely related to preneoplastic changes. Thus, Fhit loss provides a 'mutator' phenotype, a cellular environment in which mild genome instability permits clonal expansion, through proliferative advantage and escape from apoptosis, in response to pressures to survive.
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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.