gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer基因剂量、表达式和本体分析确定司机基因的致癌作用和chemoradioresistance宫颈癌.pdfVIP

Gene Dosage, Expression, and Ontology Analysis Identifies Driver Genes in the Carcinogenesis and Chemoradioresistance of Cervical Cancer 1 2 3 1 1 Malin Lando , Marit Holden , Linn C. Bergersen , Debbie H. Svendsrud , Trond Stokke , Kolbein 4 3 4,5 1 Sundfør , Ingrid K. Glad , Gunnar B. Kristensen , Heidi Lyng * 1 Department of Radiation Biology, Norwegian Radium Hospital, Oslo, Norway, 2 Norwegian Computing Center, Oslo, Norway, 3 Department of Mathematics, University of Oslo, Oslo, Norway, 4 Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo, Norway, 5 Department of Medical Informatics, University of Oslo, Oslo, Norway Abstract Integrative analysis of gene dosage, expression, and ontology (GO) data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q) associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alter