Insights on PRAME and osteosarcoma by means of gene expression profiling

Toledo, Sílvia Regina Caminada de; Zago, Marco Antônio; Oliveira, Indhira Dias; Proto‐Siqueira, Rodrigo; Okamoto, Oswaldo Keith; Severino, Patrícia; Vêncio, Ricardo Z. N.; Tesser-Gamba, Francine; Silva, Wilson A.; Moreira-Filho, Carlos Alberto; Torre, Cristiane A. Dalla; Alves, Maria Tereza Seixas; Filho, Reynaldo Jesus Garcia; Simpson, Andrew J.G.; Petrilli, Antônio Sérgio

doi:10.1007/s00776-011-0106-7

Cited by 14 publications

(12 citation statements)

References 26 publications

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“…Four of the cell lines showed simultaneously gain and two additional cell lines showed gain and over-expression. PRAME was also over-expressed in 12/29 osteosarcoma clinical samples based on identical types of microarray data (no methylation data was available) [27], and has also recently been shown by others to be over-expressed in osteosarcomas [40], [41]. Hypo-methylation of PRAME has been demonstrated to be responsible for the increased expression in various types of cancer [42].…”

Section: Discussionmentioning

confidence: 86%

Integrative Analysis Reveals Relationships of Genetic and Epigenetic Alterations in Osteosarcoma

et al. 2012

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BackgroundOsteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies.Principal FindingsThe cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression) using a recurrence threshold of 6/19 (>30%) cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2′-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes.ConclusionsIntegrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between DNA copy number, DNA methylation and mRNA expression in osteosarcomas, contributing to better understanding of osteosarcoma biology.

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Section: Discussionmentioning

confidence: 86%

Integrative Analysis Reveals Relationships of Genetic and Epigenetic Alterations in Osteosarcoma

et al. 2012

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“…The second point shows as, although a diffuse positivity for PRAME (4+) could reasonably favor a diagnosis of M in the appropriate clinical set, rare cases of M and MM could be negative for PRAME (patient #15), as well as other tumors (sarcomas, carcinomas of the female genital tracts, leukemias and germ cell tumors) could be positive for PRAME. [12][13][14][15][16][17][18][19][20] In this context, DS showing positivity for both PRAME and melanocytic markers (Melan A and HMB45) strongly encourages a diagnosis of M, especially on small/incisional biopsies with the risk that material could be consumed on serial sections. Last, DS showed more intense staining for HMB45 rather than Melan A, with Melan A being more intense in SS rather than in DS (Table 2, Fig.…”

Section: Resultsmentioning

confidence: 99%

HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)

Grillini

Ricci

Pino

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that was recently found to be expressed by malignant melanocytic lesions but not by benign ones, thus resulting useful in this diagnostic field. PRAME could also be expressed by some normal tissues and nonmelanocytic tumors, suggesting as caution should be adopted to use PRAME as a "pan-melanoma" marker for the differential diagnosis with other malignant tumors. Until now, PRAME expression was exclusively investigated through single staining with a monoclonal antibody targeting PRAME and with double staining for Melan A/PRAME found to be useful in specific diagnostic sets. Herein, we studied the expression of PRAME in 40 melanocytic lesions and 23 nonmelanocytic ones using PRAME, Melan A/ PRAME, and novel double staining for HMB45/PRAME. Although our results need to be validated, they support the adoption of HMB45/PRAME, alone or in combination with PRAME and Melan A/PRAME, as a helpful marker in the diagnosis of melanocytic neoplasms with a high concordance rate between primary melanoma and corresponding metastases.

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“…All three of them are target antigens overexpressed on tumor cells. 33 , 34 , 35 Of the 15 patients who were included in the study, 73% were defined as responders. Furthermore, 5 of the 7 WT patients who received the infusions were defined as responders.…”

Section: Immune Cell Infiltrationmentioning

confidence: 99%

Systematic review of the immunological landscape of Wilms tumors

Palmisani

Kovar

Kager

et al. 2021

Molecular Therapy - Oncolytics

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Results of immunotherapy in childhood solid cancer have been so far, with the exception of neuroblastoma, quite disappointing. Lack of knowledge of the immune contexture of these tumors may have contributed to the failure of immunotherapies so far. Here, we systematically reviewed the literature regarding the immunology of Wilms tumor (WT), one of the most frequent pediatric solid tumors of the abdomen. In Wilms tumor patients the high cure rate of >90%, achieved by the combination of surgery and radio-chemotherapy, is at the expense of a high early and late toxicity. Moreover, treatment-resistant entities, such as diffuse anaplastic tumors or recurrent disease, still pose unsolved clinical problems. Successful immunotherapy could represent a novel and possibly less-toxic treatment option. Employing the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) method of literature search, we analyzed the current knowledge of the immunological landscape of Wilms tumors in terms of tumor microenvironment, prognostic implications of single biomarkers, and immunotherapy response.

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Insights on PRAME and osteosarcoma by means of gene expression profiling

Cited by 14 publications

References 26 publications

Integrative Analysis Reveals Relationships of Genetic and Epigenetic Alterations in Osteosarcoma

Integrative Analysis Reveals Relationships of Genetic and Epigenetic Alterations in Osteosarcoma

HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)

Systematic review of the immunological landscape of Wilms tumors

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