Telomeric associations correlate with telomere length reduction and clonal chromosome aberrations in giant cell tumor of bone.

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Abstract

Giant cell tumor of bone (GCTB) is characterized cytogenetically by frequent telomeric associations (tas). To explore the mechanisms behind the formation of tas in GCTB and to investigate their karyotypic consequences, the frequencies of tas and clonal aberrations other than tas in 20 GCTBs were compared to telomere length and status, as assessed by quantitative PCR, fluorescence in situ hybridization (FISH), and expression levels of four genes involved in telomere maintenance. Based on the G-banding results, the tumors were divided into two groups, one with a high frequency of tas and one with a low frequency. Clonal aberrations were found to be restricted to the group with a high level of tas, and the same group showed a significantly larger reduction in telomere length in tumor cells compared to peripheral blood cells. Furthermore, 65 out of 66 tas analyzed by FISH were negative for telomeric sequences. The expression levels of TERT, TERF1, TERF2, and POT1 did not correlate with telomere length or the frequency of tas. Thus, the present findings provide strong support for the notion that decreased telomere length is a prerequisite for tas in GCTBs and that the clonal changes occurring in GCTBs are derived from tas.

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Subject classification (UKÄ) – MANDATORY

  • Medical Genetics

Keywords

  • Telomere-Binding Proteins: metabolism, Telomere-Binding Proteins: genetics, Telomere: metabolism, Telomerase: metabolism, Giant Cell Tumor of Bone: genetics, Telomerase: genetics, Telomeric Repeat Binding Protein 2: genetics, Telomeric Repeat Binding Protein 2: metabolism
Original languageEnglish
Pages (from-to)121-127
JournalCytogenetic and Genome Research
Volume124
Issue number2
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes