title: Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma.
abstract: We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared with activated B-cell (ABC)-DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL.
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Laura
authors.initials: L
authors.lastname: Wake
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Karen
authors.initials: K
authors.lastname: Deffenbacher
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Lachel
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rohr
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Shuangping
authors.initials: S
authors.lastname: Guo
authors.affiliation: College of Public Health, University of Nebraska Medical Center, Omaha, NE;
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Sharathkumar
authors.initials: S
authors.lastname: Bhagavathi
authors.affiliation: Department of Hematology, Aalborg University Hospital, Aalborg, Denmark;
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkaer
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: Department of Pathology and Microbiology and.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.affiliation: Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE;
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Elaine
authors.initials: E
authors.lastname: Jaffe
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ;
authors.forename: Lisa
authors.initials: L
authors.lastname: Rimsza
authors.affiliation: Department of Pathology, University of Wurzburg, Wurzburg, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Department of Clinical Pathology, Dr Margareta Fischer-Bosch-Institute of Clinical Pharmacology, Robert-Bosch-Hospital, Stuttgart, Germany;
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.affiliation: Department of Pathology, the Norwegian Radium Hospital, University of Oslo, Oslo, Norway;
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.affiliation: Hospital Clinics, University of Barcelona, Barcelona, Spain;
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.affiliation: Clinical Pathology, Oregon Health and Science University, Portland, OR;
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.affiliation: Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH;
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.affiliation: Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH;
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.affiliation: Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE;
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA; and.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.affiliation: Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Department of Pathology and Microbiology and Department of Pathology, City of Hope National Medical Center, Duarte, CA; and.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: McKeithan
authors.affiliation: Department of Pathology and Microbiology and Department of Pathology, City of Hope National Medical Center, Duarte, CA; and.
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs