Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant promoter methylation of tumor suppressor genes has not been fully investigated in pediatric tumors. Therefore, we examined the methylation status of nine genes (p16(INK4A), MGMT, GSTP1, RASSF1A, APC, DAPK, RARbeta, CDH1 and CDH13) in 175 primary pediatric tumors and 23 tumor cell lines using methylation-specific PCR. We studied the major forms of pediatric tumors--Wilms' tumor, neuroblastoma, hepatoblastoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma, retinoblastoma and acute leukemia. The most frequently methylated gene in both primary tumors and cell lines was RASSF1A (40, 86%, respectively). However, the rates of RASSF1A methylation in individual tumor types varied from 0 to 88%. RASSF1A methylation was tumor specific and was absent in adjacent non-malignant tissues. Methylation of the other genes was relatively rare in tumors and non-malignant tissues (less than 5%). Neuroblastoma patients with methylation of RASSF1A were significantly older than patients without methylation (P=0.008). There was no relationship between methylation status and other clinico-pathologic parameters. We treated six cell lines lacking RASSF1A mRNA with 5-aza-2'deoxycytidine to examine the relationship between methylation and transcriptional silencing. In five of six cell lines, restoration of RASSF1A mRNA was confirmed by RT-PCR. Our findings indicate that aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many different forms of pediatric tumors.
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PMID:Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines. 1208 24

The National Wilms Tumor Group (NWTS) presented the clinicopathological findings predicting relapse in children with stage III favorable-histology (FH) Wilms tumor (WT) treated in the NWTS-5 study. They reported that lymph node involvement and a microscopic residual tumor were highly predictive of the EFS and OS, and concluded that patients with different stage III criteria may receive different therapies. These data suggest that the current risk classification of WT is not satisfactory. Like other pediatric tumors, such as neuroblastoma and rhabdomyosarcoma, more systemic and detailed risk classification for WT should be established using various clinical and biological markers. In the previous therapeutic protocols for WT, no biological marker was used for risk classification. Therefore, it is important to identify effective biological markers related to the prognosis of WT. The presence of LOH at 1p and 16q was associated with a worse EFS and OS, and was used for risk classification to choose the treatment regimens used in the recent COG clinical trials. There are some candidate prognostic factors that can be used in the future risk classification of WT, such as the methylation status of RASSF1A. A worldwide cooperative study should be conducted in the future to confirm whether these factors are useful in the risk classification. The goal of treatment for WT is to identify approaches that provide excellent outcomes for children with low-risk tumors without the need for chemotherapy or XRT. Conversely, more aggressive therapy may be used for children with high-risk tumors in an effort to improve their survival. To meet these goals, a new effective risk classification for WT should be established via collaborative clinical trials.
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PMID:New risk classification is necessary in the treatment of Wilms tumor. 2683 22