Gene expression profiling in sarcomas

Tschoep, Katharina; Kohlmann, Alexander; Schlemmer, M.; Haferlach, Torsten; Issels, Rolf D.

doi:10.1016/j.critrevonc.2007.04.001

Cited by 69 publications

(53 citation statements)

References 79 publications

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“…This technique, introduced in 1995 [84], was shown to be applicable to musculoskeletal soft-tissue tumors [85]. However, only a few groups are using this relatively new technology to further characterize soft-tissue sarcoma.…”

Section: Molecular Characterization Of Soft-tissue Sarcomamentioning

confidence: 99%

Prognostic factors in soft-tissue sarcomas: what have we learnt?

Choong¹,

Rüdiger

2008

Expert Review of Anticancer Therapy

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Section: Molecular Characterization Of Soft-tissue Sarcomamentioning

confidence: 99%

Prognostic factors in soft-tissue sarcomas: what have we learnt?

Choong¹,

Rüdiger

2008

Expert Review of Anticancer Therapy

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“…Table 2), e.g., Goosecoid [48], SatB2 [21], MSX1 and MSX2 [49,50], DLX5 and DLX6 [51], paired related homeobox 1 [52] and SIP1/ZEB2 [53]. The cells forming the craniofacial bone are neural crest-derived [44,54] and it is worth noting that neural crest genes have been found to be upregulated in synovial sarcomas [55,56]. Interestingly, the same homeobox and BMP genes (MSX2, Iroquois homeobox protein 5, BMP-2 and -7) together with retinoic acid signaling genes identified in synovial sarcomas [55], were also expressed in the sarcomas used in this study.…”

Section: Resultsmentioning

confidence: 99%

Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas

Wensman

Göransson

Leuchowius

et al. 2008

Breast Cancer Res Treat

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The global gene expression in three types of canine mammary tumors: carcinoma, fibrosarcoma and osteosarcoma were investigated by Affymetrix gene array technology. Unsupervised clustering analysis revealed a close clustering of the respective tumor types, with fibrosarcomas clustering close to the osteosarcomas and the carcinomas clustering closer to non-malignant mammary tissues (NMTs). A number of epithelial markers were expressed in both carcinomas and NMTs, whereas the sarcomas expressed genes related to mesenchymal differentiation. A comparison of the gene expression profile of the sarcomas versus carcinoma/NMTs revealed that the sarcomas, in particular the osteosarcomas, showed a striking upregulation of a panel of homeobox genes previously linked to craniofacial bone formation. In line with this finding, osteosarcomas showed an upregulation of bone morphogenetic proteins (BMPs) and of genes associated with retinoic acid signaling. Increased homeobox gene expression in sarcomas was also confirmed at the protein level by immunohistochemical analysis of tumor tissue, and in an osteosarcoma cell line after stimulation by BMP-2. These findings suggest that the development of mammary sarcomas specifically involves triggering of a set of homeobox genes related to neural crest and craniofacial bone development.

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“…Unsupervised hierarchical clustering of STS has found clustering of histologic subtypes in some studies (26) but not in others (27). Gene signatures have been developed that are associated with extent of disease, metastasis, and response to treatment (26).…”

Section: Discussionmentioning

confidence: 99%

A phase II study of neoadjuvant bevacizumab and radiation therapy for resectable soft tissue sarcomas.

Yoon¹,

Chen²,

Karl³

et al. 2010

JCO

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Purpose-Numerous preclinical studies demonstrate that angiogenesis inhibitors can increase the efficacy of radiation therapy (RT). We sought to examine safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas (STS) and explore biomarkers for treatment response.Methods and Materials-Patients (pts) with ≥5 cm, intermediate-or high-grade STS at significant risk of local recurrence (LR) received neoadjuvant BV alone followed by BV plus RT prior to surgical resection. Correlative science studies included analysis of serial blood and tumor samples as well as serial perfusion CT scans.Results-The 20 pts had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. Neoadjuvant treatment was well tolerated with only 4 pts having grade 3 toxicities (hypertension, LFT elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 of 20 tumors (45%), which is over double the historical rate seen with RT alone. 3 pts had a complete pathologic response. Median microvessel density (MVD) decreased 53% after BV alone (p<0.05), and following combination therapy, median tumor cell proliferation decreased by 73%, apoptosis increased 10.4 fold, and blood flow, blood volume, and permeability surface area decreased by 62-72% (p<0.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. MVD and circulating progenitor cells at baseline and reduction in MVD and plasma soluble c-KIT with BV also correlated with good pathologic response (p<0.05). After a median follow-up of 20 months, only 1 patient had a LR.Conclusions-This exploratory study indicates that BV increases the efficacy of RT against STS and may reduce LR, and thus this regimen warrants further investigation. Gene expression profiles and other tissue and circulating biomarkers show promising correlations with treatment response.

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Gene expression profiling in sarcomas

Cited by 69 publications

References 79 publications

Prognostic factors in soft-tissue sarcomas: what have we learnt?

Prognostic factors in soft-tissue sarcomas: what have we learnt?

Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas

A phase II study of neoadjuvant bevacizumab and radiation therapy for resectable soft tissue sarcomas.

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