MEK1 gene mutation. Therefore, the identification of additional oncogenes such as EGFR gene mutation on which cancer cells are dependent should be required.Methods and Results : We evaluated the sensitivity to MEK inhibitors (GSK1120212 and PD0325901) in several GC cell lines in vitro and found that three cell lines were hypersensitive to the inhibitors. PCR products corresponding to MEK1 exons 3 and 6 (A) were generated from relapsed melanomas treated with AZD6244; products were pooled and interrogated by massively parallel sequencing (a single Illumina lane). The identified MAP2K1 gene mutation is a germline mutation that replaces the amino acid glutamic acid with the amino acid glycine at position 102 (written as Glu102Gly or E102G) in MEK1 protein kinase. (A) Schematic diagram of the MEK1 gene showing mutations identified 1Department of Genome Biology, Kinki University Faculty of Medicine, Further study of a larger series of pre- and posttreatment biopsies is therefore required to determine the spectrum of MEK1 mutations that have utility as predictive biomarkers. MEK1 gene exon 2 sequencing revealed a MEK1 Q56P mutation (A > C) in the OCUM-1 cell line and a MEK1 S72G mutation (A > G) in the Okajima cell line. This change likely results in increased activation of the RAS/MAPK signaling pathway in cells throughout the body. Yuan et al . Many cancers, notably melanomas, are driven by activation of the RAS-ERK signaling pathway, but tumors are often resistant to pathway-targeted therapies. Methods: We investigated the MEK1 mutation (n 280) and AKT2 mutation (n 273) in surgically treated non-small cell lung cancer cases. 1Department of Genome Biology, Kinki University Faculty of Medicine, This mutation was previously reported in a case of lung adenocarcinoma and functional studies Figure 1. An acquired MEK1 mutation in AZD6244-resistant metastatic melanoma. 26395 Ensembl ENSG00000169032 ENSMUSG00000004936 UniProt Q02750 P31938 RefSeq (mRNA) NM_002755 NM_008927 RefSeq (protein) NP_002746 NP_032953 Location (UCSC) Chr 15: 66.39 – 66.49 Mb Chr 9: 64.19 – 64.25 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene… (2007) identified heterozygous mutations in the MEK1 gene. Mutation analysis. Interestingly, 1 patient had a mutation at phe53 (F53), which is equivalent to phe57 (F57) in the MEK2 gene, where another CFC patient had a missense mutation (F57C; 601263.0001). One such mutation, MEK1(P124L), was identified in a resistant metastatic focus that emerged in a melanoma patient treated with AZD6244. It therefore seems that although some mutations in MEK1 may play a role in BRAF inhibitor resistance, the baseline presence of a MEK1 mutation is not necessarily predictive of a diminished drug response. We also for the first time demonstrated a MEK1 mutation, the K57N mutation, in melanoma. A, MEK1 Q56P mutation in the OCUM-1 cell line, MEK1 S72G mutation in the Okajima cell line, and KRAS G12V mutation in the HSC-44 cell line. To further characterize the molecular spectrum of MEK1 and MEK2 gene mutations and the phenotypic features associated with these molecular defects, we screened cohorts including patients with CFCS and NS, and carried out a detailed clinical characterization of mutation-positive cases. Detection of MEK1 mutation in melanoma and colon carcinoma. to the inhibitors; one of these cell lines had a novel MEK1 S72G mutation. MEK1. Furthermore, the role of these mutations, a xenograft study using a MEK inhibitor, and the MEK1 gene statuses of clinical samples of gastric cancer were investigated. MEK1 gene mutation in Japanese lung adenocarcinoma patients HIDEFUMI SASAKI, YU HIKOSAKA, KATSUHIRO OKUDA, OSAMU KAWANO, HARUHIRO YUKIUE, MOTOKI YANO and YOSHITAKA FUJII Department of Surgery II, Nagoya City University Medical School, Nagoya 467-8601, Japan Received October 23, 2008; Accepted December 9, 2008 DOI: 10.3892/mmr_00000076 _____ Correspondence to: … In 5 patients with CFC3, Gripp et al. The patient's genomic DNA was extracted from circulating leukocytes according to the standard procedures. The MEK1 mutation was exclusive with B-raf, K-ras, and EGFR mutation at kinase domain.


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