TY - JOUR
T1 - Telomeric associations correlate with telomere length reduction and clonal chromosome aberrations in giant cell tumor of bone.
AU - Gebre-Medhin, Samuel
AU - Broberg Palmgren, Karin
AU - Jonson, Tord
AU - Gorunova, Ludmila
AU - Vult von Steyern, Fredrik
AU - Brosjö, O
AU - Jin, Yuesheng
AU - Gisselsson Dahlén, Margareta
AU - Panagopoulos, Ioannis
AU - Mandahl, Nils
AU - Mertens, Fredrik
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Telomere-Binding Proteins: metabolism
KW - Telomere-Binding Proteins: genetics
KW - Telomere: metabolism
KW - Telomerase: metabolism
KW - Giant Cell Tumor of Bone: genetics
KW - Telomerase: genetics
KW - Telomeric Repeat Binding Protein 2: genetics
KW - Telomeric Repeat Binding Protein 2: metabolism
U2 - 10.1159/000207516
DO - 10.1159/000207516
M3 - Article
C2 - 19420923
SN - 1424-859X
VL - 124
SP - 121
EP - 127
JO - Cytogenetic and Genome Research
JF - Cytogenetic and Genome Research
IS - 2
ER -