ArticleOncogene2015
Mcph1/Brit1 deficiency promotes genomic instability and tumor formation in a mouse model.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 22 citations in OpenAlex.
- Differential sensitivity of MCPH1- and BRCA2-deficient cancer cells to PARP-1 inhibition.PloS one · 2026Article
- Review
- A telomere-related gene risk model for predicting prognosis and treatment response in acute myeloid leukemia.Heliyon · 2024Article
- The emerging role of MCPH1/BRIT1 in carcinogenesis.Frontiers in oncology · 2023Review
- Multifaceted Microcephaly-Related Gene MCPH1.Cells · 2022Review
- Bona Fide Tumor Suppressor Genes Hypermethylated in Melanoma: A Narrative Review.International journal of molecular sciences · 2021Review
- Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly.Nature communications · 2020Article
- Microcephaly family protein MCPH1 stabilizes RAD51 filaments.Nucleic acids research · 2020Article
- Analysis of the "centrosome-ome" identifies MCPH1 deletion as a cause of centrosome amplification in human cancer.Scientific reports · 2020Article
- BRIT1 dysfunction confers synergistic inhibition of hepatocellular carcinoma by targeting poly (ADP-ribose) polymerases and PI3K.American journal of cancer research · 2020Article
- Tumor suppressor MCPH1 regulates gene expression profiles related to malignant conversion and chromosomal assembly.International journal of cancer · 2019Article
- MCPH1 is essential for cellular adaptation to the GFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Silencing BRIT1 Facilitates the Abilities of Invasiveness and Migration in Trophoblast Cells.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- BRCT-domain protein BRIT1 influences class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility.PLoS genetics · 2016Article
- Chromosome structure deficiencies in MCPH1 syndrome.Chromosoma · 2015Article
- MCPH1: a window into brain development and evolution.Frontiers in cellular neuroscience · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
MCPH1, also known as BRIT1, has recently been identified as a novel key regulatory gene of the DNA damage response pathway. MCPH1 is located on human chromosome 8p23.1, where human cancers frequently show loss of heterozygosity. As such, MCPH1 is aberrantly expressed in many malignancies, including breast and ovarian cancers, and the function of MCPH1 has been implicated in tumor suppression. However, it remains poorly understood whether MCPH1 deficiency leads to tumorigenesis. Here we generated and studied both Mcph1(-/-) and Mcph1(-/-)p53(-/-) mice; we showed that Mcph1(-/-) mice developed tumors with long latency, and that primary lymphoma developed significantly earlier in Mcph1(-/-)p53(-/-) mice than in Mcph11(+/+)p53(-/-) and Mcph1(+/-)p53(-/-) mice. The Mcph1(-/-)p53(-/-) lymphomas and derived murine embryonic fibroblasts (MEFs) were both more sensitive to irradiation. Mcph1 deficiency resulted in remarkably increased chromosome and chromatid breaks in Mcph1(-/-)p53(-/-) lymphomas and MEFs, as determined by metaphase spread assay and spectral karyotyping analysis. In addition, Mcph1 deficiency significantly enhanced aneuploidy as well as abnormal centrosome multiplication in Mcph1(-/-)p53(-/-) cells. Meanwhile, Mcph1 deficiency impaired double strand break (DSB) repair in Mcph1(-/-)p53(-/-) MEFs as demonstrated by neutral Comet assay. Compared with Mcph1(+/+)p53(-/-) MEFs, homologous recombination and non-homologous end-joining activities were significantly decreased in Mcph1(-/-)p53(-/-) MEFs. Notably, reconstituted MCPH1 rescued the defects of DSB repair and alleviated chromosomal aberrations in Mcph1(-/-)p53(-/-) MEFs. Taken together, our data demonstrate MCPH1 deficiency promotes genomic instability and increases cancer susceptibility. Our study using knockout mouse models provides convincing genetic evidence that MCPH1 is a bona fide tumor suppressor gene. Its deficiency leading to defective DNA repair in tumors can be used to develop novel targeted cancer therapies in the future.
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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.