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Cytogenetics and Molecular Genetics

Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRβ locus rearrangements and putative new T-cell oncogenes

Leukemia volume 20, pages 1238–1244 (2006)Cite this article

Abstract

Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCRαδ (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH) screening for the detection of chromosomal aberrations involving the TCR loci, TCRαδ (14q11), TCRβ (7q34) and TCRγ (7p14), has not been conducted so far. Therefore, we initiated a screening of 126 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma cases and 19 T-ALL cell lines using FISH break-apart assays for the different TCR loci. Genomic rearrangements of the TCRβ locus were detected in 24/126 cases (19%), most of which (58.3%) were not detected upon banding analysis. Breakpoints in the TCRαδ locus were detected in 22/126 cases (17.4%), whereas standard cytogenetics only detected 14 of these 22 cases. Cryptic TCRαδ/TCRβ chromosome aberrations were thus observed in 22 of 126 cases (17.4%). Some of these chromosome aberrations target new putative T-cell oncogenes at chromosome 11q24, 20p12 and 6q22. Five patients and one cell line carried chromosomal rearrangements affecting both TCRβ and TCRαδ loci. In conclusion, this study presents the first inventory of chromosomal rearrangements of TCR loci in T-ALL, revealing an unexpected high number of cryptic chromosomal rearrangements of the TCRβ locus and further broadening the spectrum of genes putatively implicated in T-cell oncogenesis.

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Acknowledgements

This study was supported by the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Grants Nos. G.0310.01 and G.0106.05, and GOA, Grant No. 12051203. This text presents research results of the Belgian program of Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by the authors. BC is supported by the Belgian program of Interuniversity Poles of Attraction. We are thankful to Betty Emanuel and Nurten Yigit for excellent technical assistance.

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Authors and Affiliations

  1. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium

    B Cauwelier, B Poppe, A De Paepe & F Speleman

  2. Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France

    N Dastugue

  3. Center for Human Genetics, University of Leuven, Leuven, Belgium

    J Cools & A Hagemeijer

  4. Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium

    J Cools

  5. CHU Sart Tilman, Université de Liège, Liège, Belgium

    C Herens

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  1. B Cauwelier
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  2. N Dastugue
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Correspondence to B Cauwelier.

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Cauwelier, B., Dastugue, N., Cools, J. et al. Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRβ locus rearrangements and putative new T-cell oncogenes. Leukemia 20, 1238–1244 (2006). https://doi.org/10.1038/sj.leu.2404243

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