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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 Campo, Lisa M. Rimsza, Jan Delabie, Elaine S. Jaffe, Rita M. Braziel, Joseph M. Connors, Louis M. Staudt and Wing-Chung Chan

Key Points

  • Chromosome copy-number alterations that may affect immune surveillance and the NF-κB and p53 pathways are more frequent in tFL than FL.

  • Abnormalities involving chromosomes 6 and X are predictive of overall survival in FL.

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.

  • Submitted May 13, 2013.
  • Accepted September 1, 2013.
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