title: Clinical and molecular characterization of diffuse large B-cell lymphomas with 13q14.3 deletion.
abstract: BACKGROUND
  Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21).
  
  
  METHODS
  Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years.
  
  
  RESULTS
  Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21.
  
  
  CONCLUSIONS
  Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation.
authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Division of Hematology, Azienda Ospedaliera S. Maurizio, Bolzano/Bozen, Italy.
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authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
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authors.lastname: Scandurra
authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
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authors.lastname: Chigrinova
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska, Omaha, USA.
authors.forename: Y
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authors.lastname: Shen
authors.affiliation: Department of Pathology and Center for Experimental Research and Medical Studies, University of Turin, Turin.
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authors.affiliation: Department of Pathology and Microbiology, University of Nebraska, Omaha, USA.
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authors.affiliation: Department of Pathology and Microbiology, University of Nebraska, Omaha, USA.
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authors.affiliation: Department of Pathology and Microbiology, University of Nebraska, Omaha, USA.
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authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
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authors.affiliation: Department of Pathology and Center for Experimental Research and Medical Studies, University of Turin, Turin.
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authors.affiliation: Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan.
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authors.affiliation: Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan.
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authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine & Centro di Biotecnologie per la Ricerca Medica Applicata, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
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authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine & Centro di Biotecnologie per la Ricerca Medica Applicata, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
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authors.affiliation: Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
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authors.initials: MA
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authors.affiliation: Department of Pathology, University of Brescia, I Servizio di Anatomia Patologica, Spedali Civili di Brescia, Brescia; Division of Hematology, Spedali Civili di Brescia, Brescia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Facchetti
authors.affiliation: Department of Pathology, University of Brescia, I Servizio di Anatomia Patologica, Spedali Civili di Brescia, Brescia; Division of Hematology, Spedali Civili di Brescia, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tucci
authors.affiliation: Department of Hematology and Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: J Fr
authors.initials: JF
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authors.affiliation: Departments of Internal Medicine and Pathology, University Hospital of Bicêtre, AP/HP, Le Kremlin Bicêtre, France.
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authors.affiliation: Anatomic Pathology Unit, University of Insubria, Ospedale di Circolo, Varese, Italy.
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authors.affiliation: Anatomic Pathology Unit, University of Insubria, Ospedale di Circolo, Varese, Italy.
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authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: E
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authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Dalle Molle Institute for Artificial Intelligence (IDSIA), Manno, Switzerland.
authors.forename: I
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authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. Electronic address: frbertoni@mac.com.
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction