title: Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies.
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. 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.
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. inagel@medgen.uni-kiel.de
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: Evelyne
authors.initials: E
authors.lastname: Callet-Bauchu
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Doug
authors.initials: D
authors.lastname: Horsman
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.forename: José A
authors.initials: JA
authors.lastname: Martinez-Climent
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase