Cytogenetic-Morphologic Correlations in Aneurysmal Bone Cyst, Giant Cell Tumor of Bone and Combined Lesions. A Report from the CHAMP Study Group

Department of Pathology, University of Leuven, Belgium.
Modern Pathology (Impact Factor: 6.36). 10/2000; 13(11):1206-1210. DOI: 10.1038/modpathol.3880224

ABSTRACT Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11–13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeitnot in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11–13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.Keywords: Aneurysmal bone cyst, Chromosomes, Correlations, Cytogenetics, Giant cell tumor, Morphology

  • Source
    • "der(13)t(5;13)(q11;q14) 59, 64 À12 30LR, 68 Tarkkanen et al., 1993; Molenaar et al., 1995; McComb et al., 1996; Bay et al., 1999 tas(13;14)(p13;p13) 48, 61, 64, 65 À13 25 c , 30LR c Molenaar et al., 1995; Bay et al., 1999; Garcia et al., 2006 tas(13;15)(p13;p13) 46, 48, 49, 57, 64 À18 25 c , 82 Molenaar et al., 1995; Bay et al., 1999; Garcia et al., 2006 tas(13;19)(p13;q13) 30LR, 81 À22 68 Noguera et al., 1989; Schwartz et al., 1991; Bay et al., 1999 tas(13;21)(p13;p13) 11, 48, 52, 64 ÀY 68, 87 Sciot et al., 2000 tas(13; "
    [Show abstract] [Hide abstract]
    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.
    Genes Chromosomes and Cancer 07/2009; 48(7):583-602. DOI:10.1002/gcc.20667 · 3.84 Impact Factor
  • Source
    • "These findings suggest that chromosomal abnormalities superimposed on telomeric associations could be responsible for an aggressive clinical course in GCTB. One of the most commonly observed genetic aberrations in GCTB is TAS (Bridge et al., 1992; Sciot et al., 2000; Schwartz et al., 2002; Sawyer et al., 2005). One concept is that telomeric instability is responsible for a large degree of intratumor heterogeneity and serves as a precursor lesion to subsequent clonal structural aberrations of chromosome 11 in GCTB (Sawyer et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic instability in relation to clinical behavior was studied in 52 cases of giant cell tumor of bone (GCTB). Ploidy was determined in the mononuclear cell population by using native cell smears and image cytometry. A relocalization technique allowed fluorescent in situ hybridization (FISH) analysis of CD68-negative neoplastic cells for numerical changes of chromosomes X, 3, 4, 6, 11, and telomeric association on 11p. Genome-wide alterations were tested using array comparative genomic hybridization (array-CGH) on magnetically separated CD68-negative tumor cells. CTNNB1, TP53, and BCL2 protein expression was also analyzed in formol-paraffin sections to see if their pathways are involved in the development of chromosomal instability. CD68-positive histiocytes showed no significant numerical chromosome and telomeric alterations. Based on ploidy values and clinical outcome, we could distinguish five groups as follows: diploid nonrecurrent (n = 20), tetraploid nonrecurrent (n = 6), diploid recurrent (n = 5), tetraploid and/or aneuploid recurrent (n = 14), and malignant cases (n = 7). Random individual-cell aneusomy was significantly (P < 0.001) more frequent in the recurrent groups (36.01 +/- 11.94%) than in the benign nonrecurrent cases (10.65 +/- 3.66%). The diploid recurrent group showed significantly (P < 0.001) increased balanced aneusomy compared with the diploid nonrecurrent group and the tetraploid nonrecurrent group represented eusomic polysomy. Array-CGH and FISH showed clonal aberrations almost exclusively in the malignant group. None of the protein markers tested showed significant correlation with elevated aneuploidy/polysomy (P = 0.56). Our results show that ploidy determination combined with FISH analysis may help predicting recurrence potential of GCTB and suggest that chromosomal abnormalities superimposed on telomeric associations could be responsible for an aggressive clinical course.
    Genes Chromosomes and Cancer 03/2009; 48(6):468-79. DOI:10.1002/gcc.20656 · 3.84 Impact Factor
  • Source
    • "ic set of clonal chro - mosome aberrations ( Mitelman Database of Chromo - some Aberrations in Cancer , 2008 http : / / cgap . nci . nih . gov / Chromosomes / Mitelman ) . What has been noted by several groups , however , is that cells from GCTBs frequently display fusions between chromosome ends ( Schwartz et al . , 1989 ; Bridge et al . , 1992 ; Sciot et al . , 2000 ; Sawyer et al . , 2005 ) . As these aberrations typically are non - clonal , and as they usually do not seem to be associ - ated with loss of material from the chromosome arms involved , they are designated telomeric associations ( tas ) rather than dicentric chromosomes . Little is known about the causes and consequences of tas in GCT"
    [Show abstract] [Hide abstract]
    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.
    Cytogenetic and Genome Research 02/2009; 124(2):121-7. DOI:10.1159/000207516 · 1.91 Impact Factor
Show more