ArticlePloS one2010
CBL is frequently altered in lung cancers: its relationship to mutations in MET and EGFR tyrosine kinases.
Article in PloS one, 2010. 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 64 papers, 3 of them syntheses that pooled it.
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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
64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer.Molecular carcinogenesis · 2018Pooled it
- Functional variants in DCAF4 associated with lung cancer risk in European populations.Carcinogenesis · 2017Pooled it
- Drug repositioning discovery for early- and late-stage non-small-cell lung cancer.BioMed research international · 2014Pooled it
- MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Nonsquamous NSCLC Progressing On or After Checkpoint Inhibitor Therapy or Chemotherapy.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Trial
- THe Biom: a platform for visualization and exploration of cancer transcriptomic biomarkers identified by robust feature selection.Bioinformatics advances · 2026Article
- An Observatory for theCancers · 2023Review
- Four Immune Modulating Genes in Primary Melanoma That Predict Metastatic Potential.The Journal of surgical research · 2022Article
- MET∆14 promotes a ligand-dependent, AKT-driven invasive growth.Life science alliance · 2022Article
- The RING finger protein family in health and disease.Signal transduction and targeted therapy · 2022Review
- Review
- The Ubiquitin System: An Emerging Therapeutic Target for Lung Cancer.International journal of molecular sciences · 2021Review
- Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Co-stimulatory and co-inhibitory immune markers in solid tumors withFuture science OA · 2020Article
- Article
- Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer.Frontiers of medicine · 2020Article
- Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis.EBioMedicine · 2020Article
- Photocrosslinking Activity-Based Probes for Ubiquitin RING E3 Ligases.Cell chemical biology · 2020Article
- Epigenome-Wide Tobacco-Related Methylation Signature Identification and Their Multilevel Regulatory Network Inference for Lung Adenocarcinoma.BioMed research international · 2020Article
- EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma.Oncogenesis · 2019Article
- Loss of function Cbl-c mutations in solid tumors.PloS one · 2019Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedHsu, Han-Shui [added]
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundNon-small cell lung cancer (NSCLC) is a heterogeneous group of disorders with a number of genetic and proteomic alterations. c-CBL is an E3 ubiquitin ligase and adaptor molecule important in normal homeostasis and cancer. We determined the genetic variations of c-CBL, relationship to receptor tyrosine kinases (EGFR and MET), and functionality in NSCLC. METHODS AND
findingsUsing archival formalin-fixed paraffin embedded (FFPE) extracted genomic DNA, we show that c-CBL mutations occur in somatic fashion for lung cancers. c-CBL mutations were not mutually exclusive of MET or EGFR mutations; however they were independent of p53 and KRAS mutations. In normal/tumor pairwise analysis, there was significant loss of heterozygosity (LOH) for the c-CBL locus (22%, n = 8/37) and none of these samples revealed any mutation in the remaining copy of c-CBL. The c-CBL LOH also positively correlated with EGFR and MET mutations observed in the same samples. Using select c-CBL somatic mutations such as S80N/H94Y, Q249E and W802* (obtained from Caucasian, Taiwanese and African-American samples, respectively) transfected in NSCLC cell lines, there was increased cell viability and cell motility.
conclusionsTaking the overall mutation rate of c-CBL to be a combination as somatic missense mutation and LOH, it is clear that c-CBL is highly mutated in lung cancers and may play an essential role in lung tumorigenesis and metastasis.
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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.