Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma

Green, Michael R., Aya-Bonilla, Carlos, Gandhi, Maher K., Lea, Rod A., Wellwood, Jeremy, Wood, Peter, Marlton, Paula and Griffiths, Lyn R. (2011) Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma. Genes Chromosomes and Cancer, 50 5: 313-326. doi:10.1002/gcc.20856

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Author Green, Michael R.
Aya-Bonilla, Carlos
Gandhi, Maher K.
Lea, Rod A.
Wellwood, Jeremy
Wood, Peter
Marlton, Paula
Griffiths, Lyn R.
Title Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma
Journal name Genes Chromosomes and Cancer   Check publisher's open access policy
ISSN 1045-2257
Publication date 2011-05-01
Year available 2011
Sub-type Article (original research)
DOI 10.1002/gcc.20856
Open Access Status Not yet assessed
Volume 50
Issue 5
Start page 313
End page 326
Total pages 14
Place of publication Hoboken, NJ, U.S.A.
Publisher John Wiley & Sons, Inc.
Language eng
Abstract Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knockdown of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy. (C) 2011 Wiley-Liss, Inc.
Keyword Oncology
Genetics & Heredity
Oncology
Genetics & Heredity
GENETICS & HEREDITY
ONCOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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Created: Sat, 05 Nov 2011, 00:13:20 EST by Matthew Lamb on behalf of School of Medicine