DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

• Pediatric GCT associated with genetic susceptibility [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Will be modeled using a Poisson regression. A likelihood ratio test determines the statistical significance.
  
  

• List of genes that distinguish between the three most common histologic subtypes of pediatric GCT: yolk sac tumor, teratoma, and germinoma [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  A permutation based Chi-Square test for categorical covariates or a permutation based Kruskal-Wallis test (continuous risk factors) will be used.
  
  
• Validation of array results by pyrosequencing [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  A standard case-only approach evaluating differences in methylation by histology, age and gender will be done using chi-square and ANOVA.
  
  

OBJECTIVES:

I. To evaluate associations between genetic variation and pediatric germ cell tumor (GCT) using a case-parent triad design to identify variants in four genes, KITLG, SPRY4, BAK1, and DMRT1, associated with pediatric GCT.

II. To evaluate associations between genetic variation and pediatric GCT using a case-parent triad design to include targeted genotyping of single nucleotide polymorphisms (SNPs) in selected key pathways essential for normal in utero germ cell development, specifically genes involved in survival of germ cells during migration, apoptosis, and cell cycle control.

III. To explore inter- and intratumoral heterogeneity in DNA methylation by tumor histology.

OUTLINE: This is a multicenter study.

Patients and parents or siblings undergo saliva sample collection. DNA extracted from saliva samples and from patients' archived tumor tissue samples is genotyped and analyzed by methylation arrays, including methylation-specific polymerasechain reaction (PCR) (pyrosequencing) assays. Genetic variation between pediatric germ cell tumors and parent or sibling is also analyzed. Patients' and family members' health history, demographics, and environmental exposures are collected by questionnaires or telephone interviews. Medical history, such as chronic conditions, prescribed medications and congenital abnormalities, including cryptorchidism, is also collected. Birth characteristics of the child, including birth weight and gestational age, are also captured.