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

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.

Keywords::

• Hairy cell leukemia variant
• chromosomal translocation
• IGH
• TCL1A

Acknowledgements

This study was supported by: the Belgium Research Foundation, BIL12/Czech Republic, IWT-Flanders SBO grant no. 060848 and grant 230-2008 from Stichting tegen Kanker. P.V. is a senior clinical investigator of the Research Foundation-Flanders (FWO). H.U. was supported by a grant from the Czech Ministry of Education, Youth and Sports (MSM 6198959205).

The authors thank Pluys, R. Somers and F. Claessens for technical assistance and R. Logist for editorial help.

Potential conflict of interest

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