delineating genetic alterations for tumor progression in the mcf10a series of breast cancer cell lines描述基因改变肿瘤恶化的乳腺癌细胞系mcf10a系列.pdfVIP

Delineating Genetic Alterations for Tumor Progression in the MCF10A Series of Breast Cancer Cell Lines 1 1 1 2 1 Mitsutaka Kadota , Howard H. Yang , Bianca Gomez , Misako Sato , Robert J. Clifford , Daoud 1 3 2 1 Meerzaman , Barbara K. Dunn , Lalage M. Wakefield , Maxwell P. Lee * 1 Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America, 2 Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America, 3 Basic Prevention Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, United States of America Abstract To gain insight into the role of genomic alterations in breast cancer progression, we conducted a comprehensive genetic characterization of a series of four cell lines derived from MCF10A. MCF10A is an immortalized mammary epithelial cell line (MEC); MCF10AT is a premalignant cell line generated from MCF10A by transformation with an activated HRAS gene; MCF10CA1h and MCF10CA1a, both derived from MCF10AT xenografts, form well-differentiated and poorly-differentiated malignant tumors in the xenograft models, respectively. We analyzed DNA copy number variation using the Affymetrix 500 K SNP arrays with the goal of identifying gene-specific amplification and deletion events. In addition to a previously noted deletion in the CDKN2A locus, our studies identified MYC amplification in all four cell lines. Additionally, we found intragenic deletions in several genes, including LRP1B in MCF10CA1h and MCF10CA1a, FHIT and CDH13 in MCF10CA1h,