Original ArticlesNonrandom Pattern of Telomeric Associations in Atypical Lipomatous Tumors with Ring and Giant Marker Chromosomes
Introduction
Atypical lipomatous tumors (ALTs), including atypical lipoma and well-differentiated liposarcoma, are cytogenetically characterized by hyperdiploid karyotypes with supernumerary ring chromosomes or giant marker chromosomes, the origin of which can not be determined by chromosome banding analysis 1, 2, 3. Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have shown that they are composed, completely or partly, of chromosome 12 sequences, in particular from the segment 12q14–15; Southern blotting has shown that they are associated with low-level amplification of primarily the MDM2 gene 4, 5, 6, 7, 8. Another characteristic cytogenetic feature of a substantial proportion of ALTs is an extensive karyotypic instability; that is, no or few cells are identical [9]. However, only a few of the aberrations found in addition to the primary changes—ring and giant marker chromosomes—reach the level of clonality as defined in ISCN [10]. The nonclonal aberrations include numerical and structural changes as well as telomeric associations—chromosomal structures in which two or more chromosomes are associated or fused at their telomeres. The giant cell tumor (GCT) of bone is the only known tumor type in which telomeric associations are more frequent than in the ALT 11, 12, 13, 14.
Although the presence of multiple telomeric associations in ALTs has been noted in previous reports, these aberrations have not been specified, and no systematic study of the pattern of the telomeric involvement has been published. In the present study, we registered all clonal and nonclonal aberrations found in a consecutive series of 48 ALTs with ring or giant marker chromosomes or both. The aim was to elucidate the pattern and tumor type specificity of telomeres in associations and to determine whether (some) telomeric associations might predispose to other aberrations.
Section snippets
Materials and methods
All adipose tissue tumors with near-diploid karyotypes including ring or giant marker chromosomes or both investigated at our laboratory in a 10-year period were studied. The median age of the 48 patients was 68 (39–82) years (Table 1). Two samples from cases 4 and 108 were obtained with an interval of 6 and 2 years, respectively. Of the 50 samples, 42 were from primary tumors and 8 from local recurrences.
The samples were processed for short-term culturing and cytogenetic analysis as described
Results
Clonal karyotypic changes are presented in Table 1. Supernumerary ring chromosomes (Fig. 1) were found in 47 cases; of these cases, 5 (cases 2, 4, 61, 124, and 167) also showed small marker chromosomes that might be rings and 10 (cases 119, 143, 170–172, 175–177, 186, and 189) had giant marker chromosomes in the same clone as the rings or in separate clones. In case 178, giant marker chromosomes but no rings were found. Additional numerical and structural aberrations were found in 24 tumors. No
Discussion
The cytogenetic phenomenon of two or more chromosomes aligned end-to-end with colinear chromatids has alternatively been referred to as telomeric associations, telomeric fusions, telomeric translocations, dicentric chromosomes without any apparent loss of terminal segments, and jumping end-to-end dicentrics. These structures have been reported in, for example, lymphoblastoid cell lines 18, 19, aphidicolin exposed lymphocytes [20], SV40 transformed cell lines [[21]], and in lymphocyte cultures
Acknowledgements
This work was supported by grants from the Swedish Cancer Society.
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