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Identification of candidate B-lymphoma genes by cross-species gene expression profiling. PLoS One 2013;8(10):e76889

Date

10/17/2013

Pubmed ID

24130802

Pubmed Central ID

PMC3793908

DOI

10.1371/journal.pone.0076889

Scopus ID

2-s2.0-84885126448   8 Citations

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.

Author List

Tompkins VS, Han SS, Olivier A, Syrbu S, Bair T, Button A, Jacobus L, Wang Z, Lifton S, Raychaudhuri P, Morse HC 3rd, Weiner G, Link B, Smith BJ, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Burkitt Lymphoma
Cell Line, Tumor
Cell Proliferation
Cell Survival
Forkhead Box Protein M1
Forkhead Transcription Factors
Gene Expression Profiling
Gene Regulatory Networks
Genes, Neoplasm
Humans
Lymphoma, Large B-Cell, Diffuse
Mice
Species Specificity
Thiostrepton