Horsman, D. (D.)

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    Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies
    (American Society of Hematology, 2010) Gascoyne, R.D (R. D.); Tönnies, H. (Holger); Ammerpohl, O. (Ole); Dyer, M.J.S. (Martin J. S.); Martinez-Climent, J.A. (José Ángel); Nagel, I. (Inga); Akasaka, T. (T.); Horsman, D. (D.); Gesk, S. (Stefan); Harder, L. (Lana); Klapper, W. (Wolfram); Callet-Bauchu, E. (E.); Siebert, R. (Reiner); Szczepanowski, M. (Monika); Stilgenbauer, S. (Stepahn); Majid, A. (Aneela); Martin-Subero, J.I. (Jose Ignacio)
    Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis.