ArticleProceedings of the National Academy of Sciences of the United States of America2000
Chromosome instability contributes to loss of heterozygosity in mice lacking p53.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. 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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Who cites it
26 citing papers in PubMed, 69 citations in OpenAlex.
- Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- Escape from Cellular Senescence Is Associated with Chromosomal Instability in Oral Pre-Malignancy.Biology · 2023Review
- Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution.Cold Spring Harbor perspectives in medicine · 2017Review
- SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair.The EMBO journal · 2016Article
- Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas.Oncotarget · 2016Article
- MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.Oncotarget · 2015Article
- Oxidative stress preferentially induces a subtype of micronuclei and mediates the genomic instability caused by p53 dysfunction.Mutation research · 2014Article
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- Prdx1 deficiency in mice promotes tissue specific loss of heterozygosity mediated by deficiency in DNA repair and increased oxidative stress.Mutation research · 2012Article
- p53 null fluorescent yellow direct repeat (FYDR) mice have normal levels of homologous recombination.DNA repair · 2011Article
- A novel mouse model of cerebral cavernous malformations based on the two-hit mutation hypothesis recapitulates the human disease.Human molecular genetics · 2011Article
- Review of chromium (VI) apoptosis, cell-cycle-arrest, and carcinogenesis.Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews · 2010Review
- Mutagenesis in vivo in T cells of p21-deficient mice.Mutation research · 2009Article
- Increase in mitochondrial biogenesis, oxidative stress, and glycolysis in murine lymphomas.Free radical biology & medicine · 2009Article
- Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes.BMC molecular biology · 2006Article
- Genetics of cerebral cavernous malformations.Current neurology and neuroscience reports · 2005Review
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- Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations.The American journal of pathology · 2004Article
- Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The p53 tumor suppressor protein participates in multiple cellular processes including cell cycle checkpoints and programmed cell death. In cell lines, loss of p53 function is associated with increased genetic instability including aneuploidy, gene amplification, and point mutation. Although similar genetic instability often accompanies the progression of malignancy in tumors, its role in tumor initiation in normal cells is not clear. To study whether or not loss of p53 leads to genetic instability in normal cells in vivo, we have examined mechanisms of loss of heterozygosity (LOH) at the Aprt (adenine phosphoribsyltransferase) and flanking loci in normal fibroblasts and T lymphocytes of p53-deficient mice. Somatic cell variants that arose in vivo as a consequence of genetic or epigenetic alterations abolishing Aprt function were selected and expanded in vitro by virtue of their resistance to 2,6-diaminopurine (DAP). We observed that p53 null mice produced about three times as many DAP-resistant fibroblast colonies than wild-type mice, but the frequency of DAP-resistant T lymphocyte colonies was not significantly changed. Mitotic recombination, but not point mutation, partly accounted for the increase in the frequency of DAP-resistant fibroblasts. Most significantly, chromosome loss/duplication and interstitial deletion, which were extremely rare events in the wild-type mice, represented a significant proportion of LOH events in both fibroblasts and T lymphocytes of p53 null mice. Also, increased interstitial deletion was observed in fibroblasts of p53 heterozygous mice. These data suggest that increased genetic variation, including chromosome instability, starts at the initiation stage of tumorigenesis when functional p53 is absent or reduced.
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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.