ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Identification of a Novel Pathogenic Germline KDR Variant in Melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Clinical Management and Genetic Analysis of a Complex Case of Segmental Infantile Hemangioma with Subcutaneous Pelvic and Gluteal Tumefactions.Advances in experimental medicine and biology · 2026Article
- Genetics of ischemic stroke functional outcome.Journal of neurology · 2024Review
- Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients.Scientific reports · 2024Article
- Kinase Insert Domain Receptor Q472H Pathogenic Germline Variant Impacts Melanoma Tumor Growth and Patient Treatment Outcomes.Cancers · 2023Article
- Everolimus in combination with vandetanib in children, adolescents, and young adults: a phase I study.ESMO open · 2023Article
- VEGF Inhibitors Improve Survival Outcomes in Patients with Liver Metastases across Cancer Types-A Meta-Analysis.Cancers · 2023Review
- Microcystic stromal tumor of the ovary: a recurrent case with somatic CTNNB1 missense mutation.Virchows Archiv : an international journal of pathology · 2022Article
- Article
- Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke.Cellular and molecular neurobiology · 2021Article
- Genetic Relationship Between Endometriosis and Melanoma.Frontiers in reproductive health · 2021Article
- Molecular Screening of Small Biopsy Samples Using Next-Generation Sequencing in Korean Patients with Advanced Non-small Cell Lung Cancer: Korean Lung Cancer Consortium (KLCC-13-01).Journal of pathology and translational medicine · 2018Article
- Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Expanded molecular profiling of myxofibrosarcoma reveals potentially actionable targets.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications.Genome medicine · 2017Article
- Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours.Veterinary medicine and science · 2017Article
- Towards standardization of next-generation sequencing of FFPE samples for clinical oncology: intrinsic obstacles and possible solutions.Journal of translational medicine · 2017Article
- Article
- Targeted molecular profiling of rare genetic alterations in colorectal cancer using next-generation sequencing.Medical oncology (Northwood, London, England) · 2016Article
- Assessing Genetic Variants in Matched Biocompartments From Patients With Serous Ovarian Cancer.Technology in cancer research & treatmentArticle
- The KDR (VEGFR-2) Genetic Polymorphism Q472H and c-KIT Polymorphism M541L Are Associated With More Aggressive Behaviour in Astrocytic Gliomas.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeThe application of pan-cancer next-generation sequencing panels in the clinical setting has facilitated the identification of low frequency somatic mutations and the testing of new therapies in solid tumors using the "basket trial" scheme. However, little consideration has been given to the relevance of nonsynonymous germline variants, which are likely to be uncovered in tumors and germline and which may be relevant to prognostication and prediction of treatment response. EXPERIMENTAL
designWe analyzed matched tumor and normal DNA from 34 melanoma patients using an Ion Torrent cancer-associated gene panel. We elected to study the germline variant Q472H in the kinase insert domain receptor (KDR), which was identified in 35% of melanoma patients in both a pilot and an independent 1,223 patient cohort. Using patient-derived melanoma cell lines and human samples, we assessed proliferation, invasion, VEGF levels, and angiogenesis by analyzing tumor microvessel density (MVD) using anti-CD34 antibody.
resultsSerum VEGF levels and tumor MVD were significantly higher in Q472H versus KDR wild-type (WD) patients. Primary cultures derived from melanomas harboring the KDR variant were more proliferative and invasive than KDR wild type. Finally, using a VEGFR2 antibody, we showed that KDR Q472H cells were sensitive to targeted inhibition of VEGFR2, an effect that was not observed in KDR WT cells.
conclusionsOur data support the integration of germline analysis into personalized treatment decision-making and suggest that patients with germline KDR variant might benefit from antiangiogenesis treatment. Clin Cancer Res; 22(10); 2377-85. ©2015 AACR.
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