ArticleNeoplasia (New York, N.Y.)2010
Mutations in the c-Kit gene disrupt mitogen-activated protein kinase signaling during tumor development in adenoid cystic carcinoma of the salivary glands.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Pooled it
- Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Mechanism of immune escape mediated by receptor tyrosine kinase KIT in thyroid cancer.Immunity, inflammation and disease · 2023Article
- Characterization of ferroptosis driver gene signature in head and neck squamous cell carcinoma (HNSC).American journal of translational research · 2023Article
- The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2022Review
- Establishment and characterization of an oral tongue squamous cell carcinoma cell line from a never-smoking patient.Oral oncology · 2017Article
- Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening.International journal of oncology · 2016Article
- Molecular genetic studies on EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 in primary pulmonary adenoid cystic carcinoma.Diagnostic pathology · 2015Article
- EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- BRAF and NRAS mutations are heterogeneous and not mutually exclusive in nodular melanoma.Applied immunohistochemistry & molecular morphology : AIMM · 2015Article
- Fatty Acid binding protein 7 is a molecular marker in adenoid cystic carcinoma of the salivary glands: implications for clinical significance.Translational oncology · 2014Article
- c-Kit Expression is Rate-Limiting for Stem Cell Factor-Mediated Disease Progression in Adenoid Cystic Carcinoma of the Salivary Glands.Translational oncology · 2014Article
- Detecting protein-protein interactions based on kinase-mediated growth induction of mammalian cells.Scientific reports · 2014Article
- Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations.Histopathology · 2013Article
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
- Screening of the c-kit gene missense mutation in invasive ductal carcinoma of breast among north Indian population.Molecular biology reports · 2012Article
- The interconnectedness of cancer cell signaling.Neoplasia (New York, N.Y.) · 2011Article
- Dinosaurs and ancient civilizations: reflections on the treatment of cancer.Neoplasia (New York, N.Y.) · 2010Article
- Diagnostic reliability of c-KIT (CD117) in salivary gland tumours - A systematic review and meta-analysis.Journal of oral and maxillofacial pathology : JOMFPReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Ras/mitogen-activated protein kinase (MAPK) pathway is considered to be a positive regulator of tumor initiation, progression, and maintenance. This study reports an opposite finding: we have found strong evidence that the MAPK pathway is inhibited in a subset of adenoid cystic carcinomas (ACCs) of the salivary glands. ACC tumors consistently overexpress the receptor tyrosine kinase (RTK) c-Kit, which has been considered a therapeutic target. We performed mutational analysis of the c-Kit gene (KIT in 17 cases of ACC and found that 2 cases of ACC had distinct missense mutations in KIT at both the genomic DNA and messenger RNA levels. These mutations caused G664R and R796G amino acid substitutions in the kinase domains. Surprisingly, the mutations were functionally inactive in cultured cells. We observed a significant reduction of MAPK (ERK1/2) activity in tumor cells, as assessed by immunohistochemistry. We performed further mutational analysis of the downstream effectors in the c-Kit pathway in the genes HRAS, KRAS, NRAS, BRAF, PIK3CA, and PTEN. This analysis revealed that two ACC tumors without KIT mutations had missense mutations in either KRAS or BRAF, causing S17N K-Ras and V590I B-Raf mutants, respectively. Our functional analysis showed that proteins with these mutations were also inactive in cultured cells. This is the first time that MAPK activity from the RTK signaling has been shown to be inhibited by gene mutations during tumor development. Because ACC seems to proliferate despite inactivation of the c-Kit signaling pathway, we suggest that selective inhibition of c-Kit is probably not a suitable treatment strategy for ACC.
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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.