Recurrent breakpoints in 14q32.13/TCL1A region in mature B-cell neoplasms with villous lymphocytes

Leuk Lymphoma. 2012 Dec;53(12):2449-55. doi: 10.3109/10428194.2012.690098.

Abstract

The genetic background of mature B-cell neoplasms with villous lymphocytes is poorly understood. We identified a novel breakpoint region at 14q32.13 that was rearranged together with IGH/14q32.33 in four cases of BRAF/V600E-negative leukemia/lymphoma with villous lymphocytes carrying either t(14;14)(q32.13;q32.33) (three patients) or del(14)(q32.13q32.33) (one patient). The 14q32.13 breakpoints were mapped by fluorescence in situ hybridization (FISH) in the region harboring the TCL1A/TCL1B/TCL6 genes, known to be affected by TCRA/D-mediated t(14;14)(q11;q32)/inv(14)(q11q32) occurring in T-cell leukemia/lymphoma. To identify the target of t(14;14)(q32.13; q32.33) and del(14)(q32.13q32.33), quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 25 candidate genes located centromerically and telomerically to the 14q32.13 breakpoint was performed. Any of the analyzed genes was commonly overexpressed in the presented cases. Of note, up-regulated transcription of TCL1A was observed in two cases. In summary, we provide evidence that IGH-mediated chromosomal aberrations affecting the 14q32.13/TCL1A-TCL6 region are recurrent in mature B-cell neoplasms with villous lymphocytes. Despite extensive qRT-PCR studies, molecular consequences of these novel aberrations remain elusive.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Chromosome Aberrations*
  • Chromosome Breakpoints
  • Chromosome Deletion
  • Chromosomes, Human, Pair 14 / genetics*
  • Chromosomes, Human, Pair 4 / genetics
  • Fatal Outcome
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Lymphoma, B-Cell / genetics
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic

Substances

  • Proto-Oncogene Proteins
  • TCL1A protein, human