Nonrandom Pattern of Telomeric Associations in Atypical Lipomatous Tumors with Ring and Giant Marker Chromosomes

doi:10.1016/S0165-4608(97)00268-9

Cancer Genetics and Cytogenetics

Volume 103, Issue 1, May 1998, Pages 25-34

https://doi.org/10.1016/S0165-4608(97)00268-9 Get rights and content

Abstract

Atypical lipomatous tumors (ALTs) are cytogenetically characterized by supernumerary ring and giant marker chromosomes. Another common finding in ALT is that the tumor cells are cytogenetically heterogeneous with a variety of mostly nonclonal numerical and structural chromosome aberrations, including telomeric associations. In a series of 48 cytogenetically investigated ALTs, all chromosomal aberrations, clonal as well as nonclonal, were registered. Clonal ring chromosomes were present in 47 cases and giant markers in 11 cases. In 7 cases, 12 clonal telomeric associations were found and 37 cases showed nonclonal associations involving 344 identified telomeres. The telomere associations were nonrandomly distributed, with the telomeres of 11p, 20p, 20q, 9q, 15p, 19q, and 22q being most frequently (8.7–4.1% of all associations) involved; only Xp and Xq were never affected. The pattern of telomeric associations in ALT was compared with literature data on 47 giant cell tumors (880 telomeres), previously reported to show a nonrandom distribution of associations, and 36 sporadic cases of a variety of other human neoplasms (583 telomeres). The analysis indicated that the telomeres of 11p, 19q, and 20q are preferentially involved in associations in several tumor types. Among other structural aberrations in the ALT series, 221 nonclonal and 52 clonal breakpoints were identified, as well as 342 nonclonal and 14 clonal numerical aberrations. The combined data suggest that telomeric associations may predispose to acquired chromosome aberrations in neoplasia.

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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Original ArticlesNonrandom Pattern of Telomeric Associations in Atypical Lipomatous Tumors with Ring and Giant Marker Chromosomes

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Adv Cancer Res

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Mayo Clin Proc

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Trends Genet

Cell

Cytogenetic findings in liposarcoma correlate with histopathologic subtypes

Cancer

Combined morphologic and karyotypic study of 59 atypical lipomatous tumorsEvaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP study group)

Am J Surg Pathol

MDM2 gene amplification correlates with ring chromosomes in soft tissue tumors

Genes Chromosom Cancer

Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma

Genes Chromosom Cancer

Comparative genomic hybridization as a tool to define two distinct chromosome 12–derived amplification units in well-differentiated liposarcomas

Genes Chromosom Cancer

Comparative genomic hybridization analysis of human sarcomasI. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21–q22 in soft tissue sarcomas

Genes Chromosom Cancer

Cytogenetic aberrations in 188 benign and borderline adipose tissue tumors

Genes Chromosom Cancer

Original Articles
Nonrandom Pattern of Telomeric Associations in Atypical Lipomatous Tumors with Ring and Giant Marker Chromosomes