MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma
Cuiling Liu, Javeed Iqbal, Julie Teruya-Feldstein, Yulei Shen, Magdalena J Dabrowska, Karen Dybkaer, Megan S Lim, Roberto Piva, Antonella Barreca, Elisa Pellegrino, Elisa Spaccarotella, Cynthia M Lachel, Can Kucuk, Chun-Sun Jiang, Xiaozhou Hu, Sharathkumar Bhagvati, Timothy C Greiner, Dennis D Weisenburger, Patricia Aoun, Sherrie L Perkins, Zifen Gao, Timothy W Mckeithan, Georgio Inghiram, Wing C Chan. Peking University Health Science Center, Beijing, China; University of Nebraska Medical Center, Omaha, NE; Memorial Sloan-Kettering Cancer Center, New York, NY; Aalborg Hospital, University of Aarhus, Aarhus, Denmark; University of Torino, Torino, Italy; University of Michigan Health System, Ann Arbor, MI; University of Utah, Salt Lake City, UT
Background: Anaplastic large cell lymphomas (ALCLs) encompass two systemic diseases, ALK(+)ALCL and ALK(-)ALCL, with a broad range of morphological, immunophenotypic and clinical features, distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. Unlike B cell lymphomas, the global alteration of miRNA expression studies on ALCLs and other T-cell lymphomas are limited.
Design: Genome-wide miRNA profiling on ALK(+)ALCLs (n = 33), ALK(-)ALCLs (n = 25), AITLs (n = 9), PTCL-NOS (n = 11) and normal T-cells were performed, with 384-well format microRNA assays plates (Taqman® Array Human MicoRNA A Card, V2.0, ABI, Foster City, CA). The raw data were uploaded in BRB-ArrayTools (version 4.2.0) for normalization and identification of miRNA signatures, specific for ALK(+)ALCLs and ALK(-)ALCLs using the Bayesian algorithm.
Results: ALCLs express many of the miRNAs that are highly expressed in normal T-cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clusters of ALCLs and cases of PTCL-NOS and AITL subtype. ALK(+)ALCL and ALK(-)ALCL cases were interspersed in unsupervised analysis suggesting a close relationship; however we identified a miRNA signature of seven miRNA (five upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, and miR-135b and two down-regulated: miR-146a and miR-155) significantly associated with ALK(+)ALCL cases. In addition, an 11 miRNA signature (four up-regulated: miR-210, miR-197, miR-191, miR-512-3p and seven down-regulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-)ALCLs from other PTCLs were derived.
Conclusions: ALCLs share the expression of many miRNAs with each other and with normal T-cells, but they also have unique profiles useful in their classification and related to their biology.
Tuesday, March 5, 2013 1:45 PM
Proffered Papers: Section G, Tuesday Afternoon