Genomic Signatures of Malignant Germ Cell Tumor Progression: A Retrospective Study of Banked Specimens

OBJECTIVES:

• Explore inter-tumoral heterogeneity in DNA methylation by tumor histology.
• Determine the genomic methylation pattern in the tumors.
• Correlate methylation pattern with tumor histology and clinical characteristics.
• Carry out exome capture and massively parallel sequencing on selected germ cell tumors (GCTs) and matched normal tissue.
• Perform exome capture and Solexa sequencing on a selected set of GCTs.
• Validate candidate mutations in an independent set of tumors.
• Determine the expression profile of mRNAs, lincRNAs and microRNAs in the tumors using RNA Seq.

OUTLINE: Archived blood and tumor tissue samples are analyzed for genomic methylation pattern, exome capture and sequencing, and candidate mutations by methylation-specific PCR techniques, single nucleotide polymorphism (SNP) arrays, and Solexa sequencing methods. Results are validated by using pyrosequencing assays and primer-extension assays. Methylation pattern is also associated with each patient's tumor histology and clinical data.