Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma

Alyssa Bouska, Timothy W. McKeithan, Karen E. Deffenbacher, Cynthia Lachel, George W. Wright, Javeed Iqbal, Lynette M. Smith, Weiwei Zhang, Can Kucuk, Andrea Rinaldi, Francesco Bertoni, Jude Fitzgibbon, Kai Fu, Dennis D. Weisenburger, Timothy C. Greiner, Bhavana J. Dave, Randy D. Gascoyne, Andreas Rosenwald, German Ott, Elias CampoLisa M. Rimsza, Jan Delabie, Elaine S. Jaffe, Rita M. Braziel, Joseph M. Connors, Louis M. Staudt, Wing Chung Chan

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Follicular lymphoma (FL), the second most common type of non-Hodgkin lymphoma in the western world, is characterized by the t(14;18) translocation, which is present in up to 90% of cases. We studied 277 lymphoma samples (198 FL and 79 transformed FL [tFL]) using a single-nucleotide polymorphism array to identify the secondary chromosomal abnormalities that drive the development of FL and its transformation to diffuse large B-cell lymphoma. Common recurrent chromosomal abnormalities in FL included gains of 2, 5, 7, 6p, 8, 12, 17q, 18, 21, and X and losses on 6q and 17p. We also observed many frequent small abnormalities, including losses of 1p36.33-p36.31, 6q23.3-q24.1, and 10q23.1-q25.1 and gains of 2p16.1-p15, 8q24.13-q24.3, and 12q12-q13.13, and identified candidate genes that may be driving this selection. Recurrent abnormalities more frequent in tFL samples included gains of 3q27.3-q28 and chromosome 11 and losses of 9p21.3 and 15q. Four abnormalities, gain of X or Xp and losses of 6q23.2-24.1 or 6q13-15, predicted overall survival. Abnormalities associated with transformation of the disease likely impair immune surveillance, activate the nuclear factor-κB pathway, and deregulate p53 and B-cell transcription factors.

Original languageEnglish (US)
Pages (from-to)1681-1690
Number of pages10
JournalBlood
Volume123
Issue number11
DOIs
StatePublished - Mar 13 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Bouska, A., McKeithan, T. W., Deffenbacher, K. E., Lachel, C., Wright, G. W., Iqbal, J., Smith, L. M., Zhang, W., Kucuk, C., Rinaldi, A., Bertoni, F., Fitzgibbon, J., Fu, K., Weisenburger, D. D., Greiner, T. C., Dave, B. J., Gascoyne, R. D., Rosenwald, A., Ott, G., ... Chan, W. C. (2014). Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma. Blood, 123(11), 1681-1690. https://doi.org/10.1182/blood-2013-05-500595