mutation analysis of braf, mek1 and mek2 in 15 ovarian cancer cell lines implications for therapybraf基因突变分析,mek1 mek2 15对治疗卵巢癌细胞株的影响.pdfVIP

Mutation Analysis of BRAF, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy 1 2 1,3 1,4 Anne L. Estep , Chana Palmer , Frank McCormick , Katherine A. Rauen * 1 Comprehensive Cancer Center and Cancer Research Institute, University of California at San Francisco, San Francisco, California, United States of America, 2 Canary Foundation, San Jose, California, United States of America, 3 Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California, United States of America, 4 Department of Pediatrics, University of California at San Francisco, San Francisco, California, United States of America Background. Among gynecologic cancers, ovarian cancer is the second most common and has the highest death rate. Cancer is a genetic disorder and arises due to the accumulation of somatic mutations in critical genes. An understanding of the genetic basis of ovarian cancer has implications both for early detection and for therapeutic intervention in this population of patients. Methodology/Principal Findings. Fifteen ovarian cancer cell lines, commonly used for in vitro experiments, were screened for mutations using bidirectional direct sequencing in all coding regions of BRAF, MEK1 and MEK2. BRAF mutations were identified in four of the fifteen ovarian cancer cell lines studied. Together, these four cell lines contained four different BRAF mutations, two of which were novel. ES-2 had the common B-Raf p.V600E mutation in exon 15 and Hey contained an exon 11 missense mutation, p.G464E. The two novel B-Raf mutants identified were a 5 amino acid heterozygous deletion p.N486-P490del in OV90, and an exon 4 missense substitution p.Q201H in OVCAR 10. One of the cell lines, ES-2, contained a mutation in MEK1, specifically, a novel heterozygous mis