DNA sequence copy number increase at 8q: A potential new prognostic marker in high-grade osteosarcoma

Tarkkanen, Maija; Elomaa, Inkeri; Blomqvist, Carl; Kivioja, Aarne; Kellokumpu‐Lehtinen, Pirkko; Böhling, Tom; Valle, Julio; Knuutila, Sakari

doi:10.1002/(sici)1097-0215(19990420)84:2<114::aid-ijc4>3.0.co;2-q

Cited by 134 publications

(110 citation statements)

References 34 publications

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“…A possible explanation for these discrepancies could be the presence of unbalanced chromosomal aberrations, specifically high-level amplifications, which may significantly affect the total DNA content with less effect on the total chromosome number. This fact has to be taken into particular consideration in high-grade OS, which is a tumor characterized by a high frequency of both gains and high-level amplifications involving several chromosomes (27)(28)(29). This hypothesis was confirmed in the present study by the CGH analysis of the cell lines.…”

Section: Discussionsupporting

confidence: 78%

Simultaneous Paired Analysis of Numerical Chromosomal Aberrations and DNA Content in Osteosarcoma

et al. 2001

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Relatively little is known about the biologic relevance of numerical chromosomal changes in relation to DNA content in osteosarcoma. In this study, by using a series of human osteosarcoma cell lines, we standardized a method for the assessment, on the same nuclei specimen, of both specific chromosome copy numbers by fluorescence in situ hybridization (FISH) and the DNA content by static cytofluorometry or image cytometry. On the same cell lines, we also evaluated the DNA content by using flow cytometry and the chromosome number distribution by metaphase analysis. Comparison between these different methods showed that DNA ploidy level as determined by FISH or metaphase analysis is frequently lower than the ploidy pattern as defined by cytometric methods. By using comparative genomic hybridization, we were able to demonstrate that these discrepancies were due to the presence of several unbalanced chromosome aberrations, specifically gains and high-level amplifications, which affect the total DNA content with less effect on the total chromosome number. Thus, evaluation of DNA ploidy in osteosarcoma cells is needed for a correct interpretation of FISH or cytogenetic data concerning numerical chromosomal changes. Evaluation of tumor ploidy in a series of clinical samples demonstrated that in high-grade osteosarcoma, flow cytometry sometimes may give false results because of the presence of high proportions of contaminating, nonneoplastic cells that cannot be excluded from the flow cytometric assessment but that do not interfere with the evaluation of DNA ploidy by static cytofluorometry or image cytometry, in which only tumor cells are selected for the analysis. The possibility of using this method to evaluate, on the same nuclei sample, both specific chromosomal aberrations and DNA ploidy may allow a better determination of numerical chromosomal changes that may be relevant for the biologic behavior of osteosarcoma.

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Section: Discussionsupporting

confidence: 78%

Simultaneous Paired Analysis of Numerical Chromosomal Aberrations and DNA Content in Osteosarcoma

et al. 2001

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“…69 Furthermore, in Ewing sarcoma and related tumors, copy number increases of chromosome 8 were associated with trends towards worse metastasis-free and overall survival, 68 in osteosarcoma with a statistically significant poor metastasisfree survival, and in chondrosarcoma with shorter overall survival. 65 Our findings suggest that copy number increase at 8q24.1-q24.3 might reflect the aggressiveness and dissemination capacity of the tumor.…”

Section: Dna Copy Number Changes Associated With Metastasis In Leiomymentioning

confidence: 65%

“…[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: 81%

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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“…CGH studies have previously shown frequent gain of 8q region with controversial results as to its prognostic value. 25,26 In this chromosomal region several relevant genes for osteosarcoma are present. Gain of Myc gene have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 RPL8 is located on chromosome 8 (8q24.3). Because a gain or a polysomy of chromosome 8 could explain the over-expression of RPL8, we performed FISH analysis on the same TMA as those used for IHC.…”

Section: Immunohistochemistry On Tma Sectionsmentioning

confidence: 99%

Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2

Salas

Jézéquel²,

Campion

et al. 2009

Intl Journal of Cancer

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The therapy regimen of high-grade osteosarcoma includes chemotherapy followed by surgical resection and postoperative chemotherapy. The degree of necrosis following definitive surgery remains the only reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. The aim of this study was to find molecular markers able to classify patients with an osteosarcoma as good or poor responders to chemotherapy before beginning treatment. Gene expression screening of 20 nonmetastatic high-grade osteosarcoma patients was performed using cDNA microarray. Expression of selected relevant genes was validated using QRT-PCR. Immunohistochemistry on tissue microarrays sections of 73 biopsies was performed to investigate protein expression. Fluorescent in situ hybridization was performed for RPL8 gene. We have found that HSD17B10 gene expression was up-regulated in poor responders and that immunohistochemistry expression of HSD17B10 on biopsy before treatment was correlated to response to chemotherapy. Other results include correlation of IFITM2, IFITM3, and RPL8 gene expression to chemotherapy response. A statistical correlation was found between polysomy 8 or gain of RPL8 and good response to chemotherapy. These data suggest that HSD17B10, RPL8, IFITM2, and IFITM3 genes are involved in the response to the chemotherapy and that HSD17B10 may be a therapeutic target. RPL8 and IFITM2 may be useful in the assessment at diagnosis and for stratifying patients taking part in randomized trials. ' 2009 UICC

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DNA sequence copy number increase at 8q: A potential new prognostic marker in high-grade osteosarcoma

Cited by 134 publications

References 34 publications

Simultaneous Paired Analysis of Numerical Chromosomal Aberrations and DNA Content in Osteosarcoma

Simultaneous Paired Analysis of Numerical Chromosomal Aberrations and DNA Content in Osteosarcoma

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

Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2

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