Distinct chromosomal imbalances in pleomorphic and in high‐grade dedifferentiated liposarcomas

Rieker, Ralf J.; Joos, Stefan; Bärtsch, Christine; Willeke, Frank; Schwarzbach, Matthias; Otaño-Joos, M.; Ohl, Sybille; Högel, Josef; Lehnert, Thomas; Lichter, Peter; Otto, Herwart F.; Mechtersheimer, Gunhild

doi:10.1002/ijc.10287

Cited by 51 publications

(51 citation statements)

References 31 publications

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“…[20][21][22][23]25 Recurrent high-level amplifications on chromosome arms 5p, 17p, and Xp have also been observed in osteosarcoma, malignant fibrous histiocytoma, and liposarcoma. 51,53,65,66 Interestingly, the frequently amplified regions we observed on chromosome arms 5p, 17p, and Xp all harbor genes involved in the ubiquitin-mediated protein degradation pathway. 67 Otañ o-Joos et al 23 have described a similar pattern of chromosomal involvement.…”

Section: Similarities and Differences In Dna Sequence Copy Number Chamentioning

confidence: 82%

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

et al. 2006

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DNA copy number changes were investigated in 51 (19 uterine and 32 nonuterine) primary leiomyosarcomas by comparative genomic hybridization. The aim was to evaluate whether true biological differences exist between uterine and nonuterine leiomyosarcoma and whether changes revealed by comparative genomic hybridization have prognostic value. Genomic imbalances were found in 48 (94%) cases. The most frequent DNA copy number changes were losses in 10q (35%), 13q (57%), and 16q (41%), gains in 1q (41%), and gains and high-level amplifications in 17p (39%). Gains were nearly as frequent as losses in both uterine and nonuterine leiomyosarcoma. Correlation-based tree modeling revealed two clusters that segregated significantly a group of uterine (gains at 1q11-q24) and a group of nonuterine (losses at 13q14-q34, 16q11.1-q24, and 10q21-q26) cases. The nonuterine cluster was associated with subcutaneous origin and a trend toward increased metastasis-free survival. Further explorative analyses identified aberrations associated with shorter metastasisfree survival time, including losses at 2q32.1-q37 and gains at 8q24.1-q24.3, whereas the cases with losses at 6cen-p25 showed longer metastasis-free survival time.

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Section: Similarities and Differences In Dna Sequence Copy Number Chamentioning

confidence: 82%

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

et al. 2006

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“…In addition to these general amplifications, cancer-specific amplifications emerged in the global analysis of amplification hot spots. 2p25-p23 amplification (containing the MYCN gene) is specific to neuroblastoma (Schwab, 2004), 12p amplifications frequently appear in embryonal tumors (teratomas) and liposarcomas (Looijenga and Oosterhuis, 1999;Rieker et al, 2002), 17p amplifications are typical of some sarcomas (osteosarcoma, MFH and leiomyosarcoma) (El-Rifai et al, 1998;Weng et al, 2003;Atiye et al, 2005) and 1q21-q24 amplifications are frequent in osteosarcomas (Ozaki et al, 2002). Our findings suggest that some amplification hot spots can be used as clinical markers for cancer diagnostics and confirm the general conception that DNA amplifications are characteristic of malignant tumors, whereas benign tumors show no amplifications.…”

Section: Discussionmentioning

confidence: 99%

DNA copy number amplification profiling of human neoplasms

et al. 2006

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DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplified chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-oforigin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.

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“…In the six pleomorphic liposarcomas, the mean number of genomic imbalances was 16.3 (range [11][12][13][14][15][16][17][18][19][20][21][22][23]. Changes occurred in all chromosomes.…”

Section: Pleomorphic Liposarcomasmentioning

confidence: 99%

“…4 Investigations of liposarcomas by comparative genomic hybridization (CGH) have shown a broad scattered pattern of genomic imbalances. [9][10][11] In this study, we analyzed altogether 36 cases of four liposarcoma subtypes by CGH to identify distinct DNA sequence copy number changes in the different subtypes and to evaluate their prognostic relevance.…”

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confidence: 99%

Gains of 13q are correlated with a poor prognosis in liposarcoma

et al. 2005

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Liposarcomas are a phenotypical heterogenous group of tumors divided into four main subtypes: welldifferentiated, dedifferentiated, myxoid/round cell, and pleomorphic. The aim of this study was to compare DNA sequence copy number changes of these subtypes as investigated by comparative genomic hybridization in 36 patients. Comparative genomic hybridization revealed genomic imbalances in tumors of 27 patients (mean 5.6 imbalances per tumor). The most frequent gains were within single regions of 1q, 12q, and 13q. We found a significant correlation of poor overall survival and gain of 13q21 (P ¼ 0.0221), 13q22 (P ¼ 0.0341), 13q31 (P ¼ 0.0410), and 13q32 (P ¼ 0.0074). The univariate Cox regression analysis revealed an increased risk of tumorrelated death for patients whose liposarcomas possess with gains of 13q21 and 13q32 simultaneously (P ¼ 0.010; RR ¼ 7.1; 95% CI 1.6-31.7). Furthermore, 12 high-level amplifications were found in tumors of seven patients. In four cases 12q14-q15 and in two cases 13q32-q33 were amplified. We identified in different liposarcoma subtypes characteristic genomic changes: Gains and high-level amplifications of 12q occurred in all 11 investigated well-differentiated liposarcomas, and these changes were often present simultaneously with gains of 1q (mean 5.5 changes). In the two dedifferentiated liposarcomas, gains of 1q in both liposarcomas, and a high-level amplification of 13q were striking. Only eight of the 17 patients with myxoid/round cell liposarcomas showed changes in DNA copy number (mean 3.4 imbalances). In four of these eight cases gains of 13q occurred. The six pleomorphic liposarcomas possessed the most frequent genomic imbalances (mean number 16.3) of all liposarcoma subtypes investigated. These imbalances were in almost all chromosomal regions detected predominantly as over-representations of chromosomes 1, 5p, 13q, and 22q. Summarizing, all subtypes but well-differentiated liposarcomas showed gains of 13q, which were associated with a poor prognosis. Modern Pathology (2005) 18, 638-644, advance online publication, 12 November 2004; doi:10.1038/modpathol.3800326Keywords: CGH; gain of 13q; liposarcoma subtypes; poor prognosis Liposarcomas are the most common soft-tissue sarcomas in adults and account for approximately 20% of all mesenchymal malignancies. The WHO classification divides liposarcomas into four main histological subtypes that are correlated with degree of malignancy: well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic liposarcomas. 1 Well-differentiated liposarcomas are tumors of low degree of malignancy. When located in the subcutis, they are usually cured by local surgical resection and rarely recur. 2 Comprising 40-45% of all liposarcomas, the well-differentiated liposarcomas are thus the largest subgroup of adipocytic malignancies. Cytogenetic characteristics of well-differentiated liposarcomas are rings as well as giant marker chromosomes that contain amplified genetic material derived from chromosome region 12q13-q15 and, alternative...

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Distinct chromosomal imbalances in pleomorphic and in high‐grade dedifferentiated liposarcomas

Cited by 51 publications

References 31 publications

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

DNA copy number amplification profiling of human neoplasms

Gains of 13q are correlated with a poor prognosis in liposarcoma

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