title: Identification of candidate B-lymphoma genes by cross-species gene expression profiling.
abstract: Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome. The human and mouse lymphomas were found to have 60 concordantly deregulated genes in common, including 8 genes that Cox hazard regression analysis associated with overall survival in a published landmark dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a number of studies contending that FOXM1 is a therapeutic target in mature B cell tumors. Our findings demonstrate the value of the "mouse filter" for genomic studies of human B-lineage neoplasms for which a vast knowledge base already exists.
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Van S
authors.initials: VS
authors.lastname: Tompkins
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Han
authors.forename: Alicia
authors.initials: A
authors.lastname: Olivier
authors.forename: Sergei
authors.initials: S
authors.lastname: Syrbu
authors.forename: Thomas
authors.initials: T
authors.lastname: Bair
authors.forename: Anna
authors.initials: A
authors.lastname: Button
authors.forename: Laura
authors.initials: L
authors.lastname: Jacobus
authors.forename: Zebin
authors.initials: Z
authors.lastname: Wang
authors.forename: Samuel
authors.initials: S
authors.lastname: Lifton
authors.forename: Pradip
authors.initials: P
authors.lastname: Raychaudhuri
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: George
authors.initials: G
authors.lastname: Weiner
authors.forename: Brian
authors.initials: B
authors.lastname: Link
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Siegfried
authors.initials: S
authors.lastname: Janz
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D051379:Mice; D013045:Species Specificity; D013883:Thiostrepton / Q000494:pharmacology
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D013883:Thiostrepton