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

Blood. 2014 Mar 13;123(11):1681-90. doi: 10.1182/blood-2013-05-500595. Epub 2013 Sep 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Chromosome Aberrations*
  • Chromosomes, Human / genetics*
  • DNA Copy Number Variations / genetics*
  • DNA, Neoplasm / genetics
  • Gene Expression Profiling
  • Genome, Human*
  • Humans
  • Lymphoma, Follicular / genetics*
  • Lymphoma, Follicular / mortality
  • Lymphoma, Follicular / pathology
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Survival Rate
  • Translocation, Genetic / genetics

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm