Cytogenetic analysis of 101 giant cell tumors of bone: Nonrandom patterns of telomeric associations and other structural aberrations

Abstract

Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor with metastatic potential. We performed cytogenetic analysis on 101 GCTB from 92 patients. Karyotypes were obtained from 95 tumors, 47 of which had clonal aberrations. The majority of the cytogenetically abnormal GCTB had multiple, up to 28 per tumor, clones. Clonal telomeric associations (tas) and other structural and numerical changes were found in about 70, 60, and 30%, respectively, of clonally abnormal tumors. Forty-seven aberrations were recurrent, of which 35 are novel. The vast majority of the recurrent aberrations were tas, confirming the important role of telomeric fusions in the development of GCTB. The frequency of tas in GCTB cultures increased with passaging, suggesting a selective advantage of tas-positive cells in vitro. The termini most frequently involved in tas were 22p, 13p, 15p, 21p, 14p, 19q, 1q, 12p, 11p, and 20q. The frequency of tas (irrespective of their clonality) was significantly higher in tumors carrying clonal changes, indicating that tas are precursors of other types of aberrations. In line with this assumption, the chromosomes preferentially involved in tas in a given tumor were also the ones most often affected by other rearrangements. We did not find the previously reported amplicon in 20q11.1, assessed by fluorescence in situ hybridization in 10 tumors. Nor did we find any association between cytogenetic features and adverse clinical outcome. Thus, local recurrences probably depend more on the adequacy of surgical treatment than on the intrinsic biology of the tumors.

Smooth muscle actin expression in primary bone tumours

“…In order to determine more precisely the nature of SMAexpressing MSC, the presence (and frequency) of telomere associations in short-term MSC cultures from six GCTBs was also performed as previously described [18].…”

A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases

“…At lower frequency than telomeric associations, clonal chromosome gains, deletions and translocations can also be found in GCT of bone[14]. Translocations occur more frequently in tumors that have more telomeric associations, and they probably result from ensuing problems in separation of dicentric chromosomes during telophase[14].…”

“…At lower frequency than telomeric associations, clonal chromosome gains, deletions and translocations can also be found in GCT of bone[14]. Translocations occur more frequently in tumors that have more telomeric associations, and they probably result from ensuing problems in separation of dicentric chromosomes during telophase[14]. However, cells with chromosomal abnormalities do not have enough of a growth advantage to dominate the tumor population, and analyses of many metaphases is required to recognize that there are clonal subpopulations in the tumor[14].…”

“…Translocations occur more frequently in tumors that have more telomeric associations, and they probably result from ensuing problems in separation of dicentric chromosomes during telophase[14]. However, cells with chromosomal abnormalities do not have enough of a growth advantage to dominate the tumor population, and analyses of many metaphases is required to recognize that there are clonal subpopulations in the tumor[14]. In Goronova's study[14] there was no association between karyotype and prognosis.…”

“…However, cells with chromosomal abnormalities do not have enough of a growth advantage to dominate the tumor population, and analyses of many metaphases is required to recognize that there are clonal subpopulations in the tumor[14]. In Goronova's study[14] there was no association between karyotype and prognosis. Also, no dominant recurrent cytogenetic abnormality was seen that might give clues to pathogenesis.…”