FGFR1 over‐expression in primary rhabdomyosarcoma tumors is associated with hypomethylation of a 5′ CpG Island and abnormal expression of the AKT1, NOG, and BMP4 genes

  title={FGFR1 over‐expression in primary rhabdomyosarcoma tumors is associated with hypomethylation of a 5′ CpG Island and abnormal expression of the AKT1, NOG, and BMP4 genes},
  author={Myriam Goldstein and Isaac Meller and Avi Orr-Urtreger},
Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma likely results from abnormal proliferation and differentiation during skeletal myogenesis. Multiple genetic alterations are associated with the three RMS histopathological subtypes, embryonal, alveolar, and pleomorphic adult variant. Recently, we reported the novel amplification of the FGFR1 gene in a RMS tumor. The involvement of FGFR1 in RMS was now further studied in primary tumors and RMS cell lines by mutation screening… 

Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: An approach to identify candidate genes involved in tumor development

The ability to identify genes of potential significance in tumor development through combining genomic and transcriptomic profiles from representative cell lines with publicly available expression profiling data from primary tumors is illustrated.

Genome-wide DNA methylation studies suggest distinct DNA methylation patterns in pediatric embryonal and alveolar rhabdomyosarcomas

It is suggested that DNA methylation signatures may aid in the diagnosis and risk stratification of pediatric rhabdomyosarcoma and help identify new targets for therapy.

Dermaseptin B2’s Anti-Proliferative Activity and down Regulation of Anti-Proliferative, Angiogenic and Metastatic Genes in Rhabdomyosarcoma RD Cells in Vitro

The results of this study indicate that Dermaseptin B2 is a target molecule for signaling pathways including PI3K/AKT, RTK and NOTCH pathways that could affect the transcription of these genes and overall inhibition of cancer progression.

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines

Combination of Vincristine with TPA/GSK126, a drug combination shown to induce differentiation of RMS cell lines, is able to partially overcome MYOD1/NOG cells chemoresistance.

Epigenetic and epigenomic mechanisms shape sarcoma and other mesenchymal tumor pathogenesis.

The epigenetic activities of histone-modifying and chromatin-remodeling enzymes such as SUV39H1/KMT1A, EZH2/K MT6A and BMI1 are central to epigenetic-regulated transformation, a property the authors coin oncoepigenic.

P16 and p27 tumor suppressor gene methylation status in childhood Wilms tumor cases

The results showed that the incidence of CpG island promoter region methylation of the p16 and p27 tumor suppressor genes in Wilms tumor was low, however, larger series are needed to determine the prognostic value of DNA methylation in p16and p27 patients.

Trichostatin A Inhibits Rhabdomyosarcoma Proliferation and Induces Differentiation through MyomiR Reactivation.

Investigation of the effect of TsA on RMS cell biology suggests that it exhibits anti-cancer properties, triggers differentiation, and thereby can complement an existing spectrum of chemotherapeutics used in RMS therapy.

E2F3 promotes cancer growth and is overexpressed through copy number variation in human melanoma

It can be speculated that copy number amplification and other mechanisms result in the high expression of E2F3 in melanoma, which promotes tumor progression by involving the cell cycle.

Mechanisms of Efficacy of the FGFR1–3 Inhibitor AZD4547 in Pediatric Solid Tumor Models

Investigation of the effects of AZD4547 on neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma cells alone and in combination with STAT3 inhibition demonstrated increased efficacy and sensitivity to AZD 4547 appears to be mediated by effects on the Ras/MAPK and JAK/STAT pathways.



Novel genes implicated in embryonal, alveolar, and pleomorphic rhabdomyosarcoma: a cytogenetic and molecular analysis of primary tumors.

The authors' data suggest the involvement of genes encoding cell adhesion, cytoskeletal signaling, and transcriptional and cell cycle components in RMS tumorigenesis, including the overexpression of the AURKA gene.

Mutation and expression analyses of the MET and CDKN2A genes in rhabdomyosarcoma with emphasis on MET overexpression

The data suggest that MET plays a role in the progression of RMS, and reduced or absent expression of p16INK4A and/or p14ARF showed no significant correlation with the clinicopathological parameters, except for the age at diagnosis.

Methylation alterations of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas.

The data suggest that the methylation status of the MyoD1 upstream CpG sites may be related to rhabdomyosarcoma tumorigenesis and may have valuable implications for its differential diagnosis.

PAX7 expression in embryonal rhabdomyosarcoma suggests an origin in muscle satellite cells

It is found that upregulation of wild-type PAX3 is independent of the presence of either fusion gene and is unlikely to contribute to tumorigenesis, and upregulated PAX7 expression is almost entirely restricted to cases without PAX3-FK HR or PAX7-FKHR fusion genes and may contribute to tumors in the absence of chimaeric PAX transcription factors.

Identification of novel genes expressed during rhabdomyosarcoma differentiation using cDNA microarrays

Several new genes with potential roles in the myogenic arrest present in rhabdomyosarcoma are identified, including PTMA, and translocase of inner mitochondrial membrane 10, two genes not previously implicated in RMS, which showed reduced expression during differentiation.

Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

This study developed a method and the associated software for the comparative analysis of genomic expression in tissues and identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolars.

A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines

The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same molecular alterations as do the primary carcinomas.

Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas.

It is found that ARMS tumors expressing either PAX-FKHR gene share a common expression profile distinct from fusion-negative ARMS and from the other rhabdomyosarcoma variants, and it is observed that PAX-NKHR expression above a minimum level is necessary for the detection of this expression profile.

Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines

Findings indicate that aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many different forms of pediatric tumors.