Clinical and molecular characterization of diffuse large b-cell lymphomas with 13q14.3 deletion

M. Mian, M. Scandurra, E. Chigrinova, Y. Shen, G. Inghirami, Timothy Charles Greiner, W. C. Chan, Julie Marie Vose, M. Testoni, A. Chiappella, L. Baldini, M. Ponzoni, A. J M Ferreri, S. Franceschetti, G. Gaidano, S. Montes-Moreno, M. A. Piris, F. Facchetti, A. Tucci, J. Fr NomdedeuT. Lazure, S. Uccella, M. G. Tibiletti, E. Zucca, I. Kwee, F. Bertoni

Research output: Contribution to journalArticle

13 Citations (Scopus)

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). Patients and 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.

Original languageEnglish (US)
Pages (from-to)729-735
Number of pages7
JournalAnnals of Oncology
Volume23
Issue number3
DOIs
StatePublished - Mar 1 2012

Fingerprint

Lymphoma, Large B-Cell, Diffuse
DNA Fingerprinting
Vincristine
B-Cell Chronic Lymphocytic Leukemia
Prednisone
Cell Cycle Checkpoints
MicroRNAs
Cyclophosphamide
Genes
Real-Time Polymerase Chain Reaction
Down-Regulation
Genome
Gene Expression

Keywords

  • Cell cycle
  • Immune escape
  • Lymphoma
  • Microarray
  • R-CHOP

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Clinical and molecular characterization of diffuse large b-cell lymphomas with 13q14.3 deletion. / Mian, M.; Scandurra, M.; Chigrinova, E.; Shen, Y.; Inghirami, G.; Greiner, Timothy Charles; Chan, W. C.; Vose, Julie Marie; Testoni, M.; Chiappella, A.; Baldini, L.; Ponzoni, M.; Ferreri, A. J M; Franceschetti, S.; Gaidano, G.; Montes-Moreno, S.; Piris, M. A.; Facchetti, F.; Tucci, A.; Nomdedeu, J. Fr; Lazure, T.; Uccella, S.; Tibiletti, M. G.; Zucca, E.; Kwee, I.; Bertoni, F.

In: Annals of Oncology, Vol. 23, No. 3, 01.03.2012, p. 729-735.

Research output: Contribution to journalArticle

Mian, M, Scandurra, M, Chigrinova, E, Shen, Y, Inghirami, G, Greiner, TC, Chan, WC, Vose, JM, Testoni, M, Chiappella, A, Baldini, L, Ponzoni, M, Ferreri, AJM, Franceschetti, S, Gaidano, G, Montes-Moreno, S, Piris, MA, Facchetti, F, Tucci, A, Nomdedeu, JF, Lazure, T, Uccella, S, Tibiletti, MG, Zucca, E, Kwee, I & Bertoni, F 2012, 'Clinical and molecular characterization of diffuse large b-cell lymphomas with 13q14.3 deletion', Annals of Oncology, vol. 23, no. 3, pp. 729-735. https://doi.org/10.1093/annonc/mdr289
Mian, M. ; Scandurra, M. ; Chigrinova, E. ; Shen, Y. ; Inghirami, G. ; Greiner, Timothy Charles ; Chan, W. C. ; Vose, Julie Marie ; Testoni, M. ; Chiappella, A. ; Baldini, L. ; Ponzoni, M. ; Ferreri, A. J M ; Franceschetti, S. ; Gaidano, G. ; Montes-Moreno, S. ; Piris, M. A. ; Facchetti, F. ; Tucci, A. ; Nomdedeu, J. Fr ; Lazure, T. ; Uccella, S. ; Tibiletti, M. G. ; Zucca, E. ; Kwee, I. ; Bertoni, F. / Clinical and molecular characterization of diffuse large b-cell lymphomas with 13q14.3 deletion. In: Annals of Oncology. 2012 ; Vol. 23, No. 3. pp. 729-735.
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T1 - Clinical and molecular characterization of diffuse large b-cell lymphomas with 13q14.3 deletion

AU - Mian, M.

AU - Scandurra, M.

AU - Chigrinova, E.

AU - Shen, Y.

AU - Inghirami, G.

AU - Greiner, Timothy Charles

AU - Chan, W. C.

AU - Vose, Julie Marie

AU - Testoni, M.

AU - Chiappella, A.

AU - Baldini, L.

AU - Ponzoni, M.

AU - Ferreri, A. J M

AU - Franceschetti, S.

AU - Gaidano, G.

AU - Montes-Moreno, S.

AU - Piris, M. A.

AU - Facchetti, F.

AU - Tucci, A.

AU - Nomdedeu, J. Fr

AU - Lazure, T.

AU - Uccella, S.

AU - Tibiletti, M. G.

AU - Zucca, E.

AU - Kwee, I.

AU - Bertoni, F.

PY - 2012/3/1

Y1 - 2012/3/1

N2 - 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). Patients and 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.

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KW - Immune escape

KW - Lymphoma

KW - Microarray

KW - R-CHOP

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