ArticleOncotarget2015
FHIT loss-induced DNA damage creates optimal APOBEC substrates: Insights into APOBEC-mediated mutagenesis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential.Journal of hematology & oncology · 2023Review
- Review
- The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead.Open biology · 2020Article
- Correlation of gene expression and associated mutation profiles of APOBEC3A, APOBEC3B, REV1, UNG, and FHIT with chemosensitivity of cancer cell lines to drug treatment.Human genomics · 2018Article
- The ubiquitous 'cancer mutational signature' 5 occurs specifically in cancers with deletedOncotarget · 2017Article
- Enzyme cycling contributes to efficient induction of genome mutagenesis by the cytidine deaminase APOBEC3B.Nucleic acids research · 2017Article
- APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.Nature communications · 2017Article
- Identification of Fhit as a post-transcriptional effector of Thymidine Kinase 1 expression.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Article
- Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors.Nature genetics · 2016Article
- Somatic TP53 Mutations in the Era of Genome Sequencing.Cold Spring Harbor perspectives in medicine · 2016Review
- Fhit loss-associated initiation and progression of neoplasia in vitro.Cancer science · 2016Article
- APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication.Cell reports · 2016Article
- High content screening application for cell-type specific behaviour in heterogeneous primary breast epithelial subpopulations.Breast cancer research : BCR · 2016Article
- Degradation of the cancer genomic DNA deaminase APOBEC3B by SIV Vif.Oncotarget · 2015Article
- The eQTL-missense polymorphisms of APOBEC3H are associated with lung cancer risk in a Han Chinese population.Scientific reports · 2015Article
- An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers.Nature genetics · 2015Article
- Effect of apolipoprotein B mRNA-editing catalytic polypeptide-like protein-3G in cervical cancer.International journal of clinical and experimental pathology · 2015Article
- AID/APOBEC deaminases and cancer.Oncoscience · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
APOBEC cytidine deaminase activity is a major source of hypermutation in cancer. But previous studies have shown that the TC context signature of these enzymes is not observed in sizable fractions of cancers with overexpression of APOBEC, suggesting that cooperating factors that contribute to this mutagenesis should be identified. The fragile histidine triad protein (Fhit) is a tumor suppressor and DNA caretaker that is deleted or silenced in >50% of cancers. Loss of Fhit protein activity causes replication stress through reduced Thymidine Kinase 1 expression, increased DNA breaks, and global genome instability in normal and cancer cells. Using data from The Cancer Genome Atlas (TCGA), we show that FHIT-low/APOBEC3B-high expressing lung adenocarcinomas display significantly increased numbers of APOBEC signature mutations. Tumor samples in this cohort with normal FHIT expression do not exhibit APOBEC hypermutation, despite having high APOBEC3B expression. In vitro, silencing Fhit expression elevates APOBEC3B-directed C > T mutations in the TP53 gene. Furthermore, inhibition of Fhit loss-induced DNA damage via thymidine supplementation decreases the TP53 mutation burden in FHIT-low/APOBEC3B-high cells. We conclude that APOBEC3B overexpression and Fhit-loss induced DNA damage are independent events that, when occurring together, result in a significantly increased frequency of APOBEC-induced mutations that drive cancer progression.
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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.