Mutation Analysis of BRAF, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy

摘要: Background. Among gynecologic cancers, ovarian cancer is the second most common and has highest death rate. Cancer a genetic disorder arises due to accumulation of somatic mutations in critical genes. An understanding basis implications both for early detection therapeutic intervention this population patients. Methodology/Principal Findings. Fifteen cell lines, commonly used vitro experiments, were screened using bidirectional direct sequencing all coding regions BRAF, MEK1 MEK2. BRAF identified four fifteen lines studied. Together, these contained different mutations, two which novel. ES-2 had B-Raf p.V600E mutation exon 15 Hey an 11 missense mutation, p.G464E. The novel mutants 5 amino acid heterozygous deletion p.N486-P490del OV90, 4 substitution p.Q201H OVCAR 10. One ES-2, MEK1, specifically, substitution, p.D67N resulted from nt 199 GRA transition. None region Functional characterization mutant by transient transfection with subsequent Western blot analysis demonstrated increased ERK phosphorylation as compared controls. Conclusions/Significance. In study, we report 12 also first associated human cancer. data indicate may confer alteration activation through MAPK pathway. significance findings that MEK1/2 be more than anticipated could have important treatment patients disease suggests potential new avenues.