High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

Leukemia. 2008 Oct;22(10):1891-8. doi: 10.1038/leu.2008.191. Epub 2008 Jul 17.

Abstract

Angioimmunoblastic T-cell lymphoma (AILT) and peripheral T-cell lymphoma, unspecified (PTCL-u) are relatively frequent subtypes of T- or natural killer cell lymphoma. To characterize the structural anomalies of chromosomes associated with these disorders, we here determined chromosome copy number alterations (CNAs) and loss of heterozygosity (LOH) at >55,000 single nucleotide polymorphism loci for clinical specimens of AILT (n=40) or PTCL-u (n=33). Recurrent copy number gain common to both conditions was detected on chromosomes 8, 9 and 19, whereas common LOH was most frequent for a region of chromosome 2. AILT- or PTCL-u-specific CNAs or LOH were also identified at 21 regions, some spanning only a few hundred base pairs. We also identified prognosis-related CNAs or LOH by several approaches, including Cox's proportional hazard analysis. Among the genes that mapped to such loci, a poor prognosis was linked to overexpression of CARMA1 at 7p22 and of MYCBP2 at 13q22, with both genes being localized within regions of frequent copy number gain. For a frequent LOH region at 2q34, we also identified IKAROS family zinc-finger 2 cDNAs encoding truncated proteins. Our data indicate that AILT and PTCL-u consist of heterogeneous subgroups with distinct transforming genetic alterations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CARD Signaling Adaptor Proteins / genetics
  • Chromosome Aberrations*
  • DNA-Binding Proteins / genetics
  • Female
  • Guanylate Cyclase / genetics
  • Humans
  • Ikaros Transcription Factor / genetics
  • Loss of Heterozygosity*
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / mortality
  • Lymphoma, T-Cell, Peripheral / genetics*
  • Lymphoma, T-Cell, Peripheral / mortality
  • Male
  • Middle Aged
  • Neprilysin / analysis
  • Oligonucleotide Array Sequence Analysis*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Transcription Factors / genetics

Substances

  • CARD Signaling Adaptor Proteins
  • DNA-Binding Proteins
  • IKZF2 protein, human
  • MYCBP protein, human
  • Transcription Factors
  • Ikaros Transcription Factor
  • Neprilysin
  • CARD11 protein, human
  • Guanylate Cyclase