Biomarkers in Patients With Rhabdomyosarcoma
RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.
PURPOSE: This research study is studying biomarkers in patients with rhabdomyosarcoma.
Genetic: DNA methylation analysis
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis
|Official Title:||Integrative Epigenomic Approach to Gene Discovery in Rhabdomyosarcoma (RMS)|
- Genome-wide alterations in DNA methylation in ARMS and ERMS [ Designated as safety issue: No ]
- Genome-wide DNA copy number alterations in ARMS and ERMS [ Designated as safety issue: No ]
- Pathogenic genes and pathways by integrative genomic analysis [ Designated as safety issue: No ]
|Study Start Date:||October 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
- Determine genome-wide alterations in DNA methylation in ARMS and ERMS.
- Determine genome-wide DNA copy number alterations in ARMS and ERMS.
- Determine pathogenic genes and pathways by integrative genomic analysis.
OUTLINE: Genome-wide DNA-methylation analysis on ARMS, ERMS, and normal human skeletal myoblasts will be conducted using the HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR) assay. The methylation status of 1.3 million CpGs at promoters, gene bodies, and intergenic areas will be analyzed. Parallel gene expression analysis will be done and correlated with changes in methylation to uncover genes regulated by epigenetic alterations and altered by genomic losses or gains.
Genes that are altered by both genetic and epigenetic alterations in different sets of patients will be selected by the MIGHT (Multi-dimensional Integration of Genomic data from Human Tissues) algorithm to uncover new genes that are potentially involved in the pathogenesis of ARMS and ERMS. Gene ontology, pathway, and DNA motif analysis algorithms, and other computational approaches will be used to determine the biological consequences of the changes. Prioritized set of epigenetic and genetic alterations will be validated by bisulfite MassArray, FISH, and qRT-PCR in larger numbers of ARMS and ERMS samples.
|Principal Investigator:||Caroline Y. Hu, MD||Tomorrows Children's Institute at Hackensack University Medical Center|