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

Yale University, New Haven, Connecticut, United States
Modern Pathology (Impact Factor: 6.19). 10/2000; 13(11):1206-1210. DOI: 10.1038/modpathol.3880224


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

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Available from: Paola Dal Cin, Apr 18, 2014
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    • "Telomeric associations (TAS) have been reported as one of the most common genetic aberrations in GCT (4–6). It has been proposed that telomeric instability is responsible for a large degree of intra-tumor heterogeneity and the telomere serves as a precursor lesion to subsequent clonal structural aberrations of chromosome 11 in GCT. "
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    ABSTRACT: Giant cell tumor of bone (GCT) is a destructive neoplasm of uncertain etiology that affects the epiphyseal ends of long bones in young adults. GCT stromal cells (GCTSCs) are the primary neoplastic cells of this tumor and are the only proliferating cell component in long-term culture, which recruits osteoclast-like giant cells that eventually mediate bone destruction. The oncogenesis of GCT and factors driving the neoplastic stromal cells to proliferate extensively and pause at an early differentiation stage of pre-osteoblast lineage remain unknown. Overexpression of p63 was observed in GCTSCs and there is growing evidence that p63 is involved in oncogenesis through different mechanisms. This study aimed to understand the specific role of p63 in cell proliferation and oncogenesis of GCTSCs. We confirmed p63 expression in the mononuclear cells in GCT by immunohistochemical staining. By real-time PCR analysis, we showed a higher level (>15‑fold) of TAp63 expression in GCTSCs compared to that in mesenchymal stem cells. Furthermore, we observed that knockdown of the p63 gene by siRNA transfection greatly reduced cell proliferation and induced cell cycle arrest at S phase in GCTSCs. We found that the mRNA expression of CDC2 and CDC25C was substantially suppressed by p63 knockdown at 24-72 h. Moreover, p63 was found to be recruited on the regulatory regions of CDC2 and CDC25C, which contain p53-responsive elements. In summary, our data suggest that p63 regulates GCTSC proliferation by binding to the CDC2 and CDC25C p53-REs, which may inhibit the p53 tumor suppressor activity and contribute to GCT tumorigenesis.
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    • "Although ABCs are known to be non-neoplastic and probably reactive lesions, more recent studies have shown that at least some of the ABCs of all types are of a neoplastic nature, owing to clonal chromosomal aberrations [6,18,19]. Recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs [5,6,19]. "
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    • "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; "
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