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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6681-6690. Prepublished online as a Blood First Edition Paper on March 10, 2009; DOI 10.1182/blood-2009-01-202028. This Article Full Text (PDF) Supplemental Methods and Tables Additional Supplemental Tables and Supplemental Figures Additional Supplemental Figures All Versions of this Article: blood-2009-01-202028v1 113/26/6681    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, C. Articles by Aguiar, R. C. T. Search for Related Content PubMed PubMed Citation Articles by Li, C. Articles by Aguiar, R. C. T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 28, 2009 Accepted March 1, 2009 Copy number abnormalities, MYC activity and the genetic fingerprint of normal B-cells mechanistically define the microRNA profile of DLBCL Cheng Li, Sang-Woo Kim, Deepak Rai, Aswani R. Bolla, Siddharth Adhvaryu, Marsha C. Kinney, Ryan S. Robetorye, and Ricardo C. T. Aguiar* Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States Division of Hematology and Medical Oncology, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States * Corresponding author; email: aguiarr{at}uthscsa.edu. MicroRNA (miRNA) deregulation contributes to cancer pathogenesis. However, analysis of miRNAs in diffuse large B-cell lymphoma (DLBCL) has been hindered by a focus on cell lines, limited number of miRNAs examined and lack of copy number data. To address these restrictions, we investigated genome-wide miRNA expression and copy number data in 86 DLBCLs. Permutation analysis showed that 63 miRNAs were recurrently disrupted in DLBCL, including highly expressed oncomirs not previously linked to chromosomal abnormalities. Further, using training and validation tumor groups, we defined a collection of miRNAs that robustly segregates DLBCLs into three subsets, which are independent of the cell-of-origin classification, extent of T-cell infiltrate and tumor site. Instead, these unique miRNA-driven DLBCL subgroups showed markedly different MYC transcriptional activity, which explained the dominance of miRNAs regulated by MYC in their expression signatures. Additionally, analysis of miRNA expression patterns of normal B-cells, and integration of copy number and expression data, demonstrated that genomic abnormalities and the genetic fingerprint of non-malignant cells also contribute to the miRNA profile of DLBCL. In conclusion, we created a comprehensive map of the miRNA genome in DLBCL, and in the process, have uncovered and mechanistically elucidated the basis for additional molecular heterogeneity in this tumor CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Micro-classifying diffuse large B-cell lymphomas Wayne Tam Blood 2009 113: 6506-6507. [Full Text] [PDF] This article has been cited by other articles: M. R. McKeller, R. S. Robetorye, P. L. M. Dahia, and R. C. T. Aguiar Integrity of the CBL gene in mature B-cell malignancies Blood, November 5, 2009; 114(19): 4321 - 4322. [Full Text] [PDF] W. Tam Micro-classifying diffuse large B-cell lymphomas Blood, June 25, 2009; 113(26): 6506 - 6507. [Full Text] [PDF]

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