ArticleOncogene2004
Alternative splicing and mutation status of CHEK2 in stage III breast cancer.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 83 citations in OpenAlex.
- Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer.Breast cancer research : BCR · 2012Trial
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- Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?Cancers · 2022Review
- Acetylation dependent translocation of EWSR1 regulates CHK2 alternative splicing in response to DNA damage.Oncogene · 2022Article
- Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Review
- Characterization of genetic predisposition to molecular subtypes of breast cancer in Brazilian patients.Frontiers in oncology · 2022Article
- Recurrent Germline Mutations of CHEK2 as a New Susceptibility Gene in Patients with Pheochromocytomas and Paragangliomas.International journal of endocrinology · 2021Article
- Review
- Systematic Profiling of Alternative mRNA Splicing Signature for Predicting Glioblastoma Prognosis.Frontiers in oncology · 2019Article
- Article
- Genetic and epigenetic analyses guided by high resolution whole-genome SNP array reveals a possible role ofOncotarget · 2018Article
- High PTEN gene expression is a negative prognostic marker in human primary breast cancers with preserved p53 function.Breast cancer research and treatment · 2017Article
- Article
- Prevalence of theHereditary cancer in clinical practice · 2016Article
- Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth.Cancer research · 2015Article
- Genomic profiling of CHEK2*1100delC-mutated breast carcinomas.BMC cancer · 2015Article
- MicroRNA-191 promotes osteosarcoma cells proliferation by targeting checkpoint kinase 2.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Article
- RNA splicing: a new player in the DNA damage response.International journal of cell biology · 2013Review
- Malfunctioning DNA damage response (DDR) leads to the degeneration of nigro-striatal pathway in mouse brain.Journal of molecular neuroscience : MN · 2012Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DNA damage checkpoint kinase, CHK2, promotes growth arrest or apoptosis through phosphorylating targets such as Cdc25A, Cdc25C, BRCA1, and p53. Both germline and somatic loss-of-function CHEK2 mutations occur in human tumours, the former linked to the Li-Fraumeni syndrome, and the latter found in diverse types of sporadic malignancies. Here we examined the status of CHK2 by genetic and immunohistochemical analyses in 53 breast carcinomas previously characterized for TP53 status. We identified two CHEK2 mutants, 470T>C (Ile157Thr), and a novel mutation, 1368insA leading to a premature stop codon in exon 13. The truncated protein encoded by CHEK2 carrying the 1368insA was stable yet mislocalized to the cytoplasm in tumour sections and when ectopically expressed in cultured cells. Unexpectedly, we found CHEK2 to be subject to extensive alternative splicing, with some 90 splice variants detected in our tumour series. While all cancers expressed normal-length CHEK2 mRNA together with the spliced transcripts, we demonstrate and/or predict some of these splice variants to lack CHK2 function and/or localize aberrantly. We conclude that cytoplasmic sequestration may represent a novel mechanism to disable CHK2, and propose to further explore the significance of the complex splicing patterns of this tumour suppressor gene in oncogenesis.
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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.