Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies

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BlankBlood First Edition Paper, prepublished online May 11, 2010; DOI

10.1182/blood-2009-09-240440.

Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal

translocations in B-cell malignancies

Inga Nagel1,*, Monika Szczepanowski2, José I. Martín-Subero1, Lana Harder1,

Takashi Akasaka3, Ole Ammerpohl1, e Callet-Bauchu4, Randy D. Gascoyne5,

Stefan Gesk1, Horsman5, Wolfram Klapper2, Aneela Majid3, José A.

ez-Climent6, Stephan Stilgenbauer7, Holger Tönnies1, JS Dyer3 and

Reiner Siebert1

1 Institute of Human Genetics, Christian-Albrechts University Kiel & University

Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; 2 Department of

Pathology and Lymph Node Registry, University Hospital Schleswig-Holstein,

Campus Kiel, Kiel, Germany; 3 MRC Toxicology Unit, University of Leicester,

Leicester, United Kingdom; 4 Service d'Hematologie Biologique, Centre

Hospitalier Lyon Sud, Lyon, France; 5 Department of Pathology, Centre for

Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada; 6 Division

of Oncology, Center for Applied Medical Research (CIMA), University of Navarra,

Pamplona, Spain; 7 Department of Internal Medicine III, University of Ulm, Ulm,

Germany

* Corresponding author; email: inagel@...

Abstract

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. Additionally, 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.