ArticleOncogene2012
CHEK2 genomic and proteomic analyses reveal genetic inactivation or endogenous activation across the 60 cell lines of the US National Cancer Institute.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- A missense variant effect map for the human tumor-suppressor protein CHK2.American journal of human genetics · 2024Article
- Status of CHEK2 and p53 in patients with early-onset and conventional gastric cancer.Oncology letters · 2021Article
- Sensitivity of cells to ATR and CHK1 inhibitors requires hyperactivation of CDK2 rather than endogenous replication stress or ATM dysfunction.Scientific reports · 2021Article
- Review
- Versatile in vivo regulation of tumor phenotypes by dCas9-mediated transcriptional perturbation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Targeting of Chk2 as a countermeasure to dose-limiting toxicity triggered by topoisomerase-II (TOP2) poisons.Oncotarget · 2016Article
- CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis.International journal of clinical and experimental medicine · 2015Article
- CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer.Prostate cancer · 2014Review
- Transcription poisoning by Topoisomerase I is controlled by gene length, splice sites, and miR-142-3p.Cancer research · 2013Article
- The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology.Cancer research · 2013Article
- Phenotypic and Molecular Characterization of MCF10DCIS and SUM Breast Cancer Cell Lines.International journal of breast cancer · 2013Article
- CellMiner: a web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set.Cancer research · 2012Article
- DNA damage response pathways and cell cycle checkpoints in colorectal cancer: current concepts and future perspectives for targeted treatment.Current cancer drug targets · 2012Review
- Article
- Functional categories associated with clusters of genes that are co-expressed across the NCI-60 cancer cell lines.PloS one · 2012Article
- Structural characterization of inhibitor complexes with checkpoint kinase 2 (Chk2), a drug target for cancer therapy.Journal of structural biology · 2011Article
- X-ray structures of checkpoint kinase 2 in complex with inhibitors that target its gatekeeper-dependent hydrophobic pocket.FEBS letters · 2011Article
- Trial Watch: Targeting ATM-CHK2 and ATR-CHK1 pathways for anticancer therapy.Molecular & cellular oncologyReview
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
CHEK2 encodes a serine/threonine kinase (Chk2) activated by ATM in response to DNA double-strand breaks. On the one hand, CHEK2 has been described as a tumor suppressor with proapoptotic, cell-cycle checkpoint and mitotic functions. On the other hand, Chk2 is also commonly activated (phosphorylated at T68) in cancers and precancerous lesions. Here, we report an extensive characterization of CHEK2 across the panel of 60 established cancer cell lines from the NCI Anticancer Screen (the NCI-60) using genomic and proteomic analyses, including exon-specific mRNA expression, DNA copy-number variation (CNV) by aCGH, exome sequencing, as well as western blot analyses for total and activated (pT68-Chk2) Chk2. We show that the high heterogeneity of Chk2 levels in cancer cells is primarily due to its inactivation (owing to low gene expression, alternative splicing, point mutations, copy-number alterations and premature truncation) or reduction of protein levels. Moreover, we observe that a significant percentage of cancer cells (12% of the NCI-60 and HeLa cells) show high endogenous Chk2 activation, which is always associated with p53 inactivation, and which is accompanied by downregulation of the Fanconi anemia and homologous recombination pathways. We also report the presence of activated Chk2 (pT68-Chk2) along with histone γ-H2AX in centrosomes.
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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.