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Genomic instability in giant cell tumor of bone. A study of 52 cases using DNA ploidy, relocalization FISH, and array-CGH analysis.
- Source :
-
Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2009 Jun; Vol. 48 (6), pp. 468-79. - Publication Year :
- 2009
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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.
- Subjects :
- Adolescent
Adult
Aged
Antigens, CD genetics
Antigens, CD metabolism
Antigens, Differentiation, Myelomonocytic genetics
Antigens, Differentiation, Myelomonocytic metabolism
Centromere metabolism
Chi-Square Distribution
Chromosomes, Human, Pair 11
Comparative Genomic Hybridization
Female
Giant Cell Tumor of Bone metabolism
Giant Cell Tumor of Bone pathology
Humans
In Situ Hybridization, Fluorescence
Male
Middle Aged
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Telomere genetics
Telomere metabolism
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
beta Catenin genetics
beta Catenin metabolism
Bone Neoplasms genetics
Genomic Instability
Giant Cell Tumor of Bone genetics
Ploidies
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2264
- Volume :
- 48
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Genes, chromosomes & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 19242928
- Full Text :
- https://doi.org/10.1002/gcc.20656