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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Molecular Epidemiology of Pediatric Germ Cell Tumors

Brief Summary: This research trial studies deoxyribonucleic acid (DNA) samples from younger patients with germ cell tumor and their parents or siblings. Studying samples of tumor tissue and saliva from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

Detailed Summary:

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.


Sponsor: Children's Oncology Group

Current Primary Outcome: Pediatric GCT associated with genetic susceptibility [ Time Frame: Up to 5 years ]

Will be modeled using a Poisson regression. A likelihood ratio test determines the statistical significance.


Original Primary Outcome: Pediatric GCT associated with genetic susceptibility

Current Secondary Outcome:

  • 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 ]
    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 ]
    A standard case-only approach evaluating differences in methylation by histology, age and gender will be done using chi-square and ANOVA.


Original Secondary Outcome: List of genes that distinguish between the three most common histologic subtypes of pediatric GCT: yolk sac tumor, teratoma, and germinoma

Information By: Children's Oncology Group

Dates:
Date Received: September 13, 2011
Date Started: November 2011
Date Completion:
Last Updated: October 5, 2016
Last Verified: October 2016