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

Completed
Conditions
Childhood Malignant Testicular Germ Cell Tumor
Testicular Yolk Sac Tumor
Ovarian Embryonal Carcinoma
Testicular Embryonal Carcinoma
Testicular Teratoma
Childhood Malignant Ovarian Germ Cell Tumor
Ovarian Mixed Germ Cell Tumor
Ovarian Teratoma
Ovarian Yolk Sac Tumor
Testicular Seminoma
Interventions
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
Registration Number
NCT01434355
Lead Sponsor
Children's Oncology Group
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 Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
932
Inclusion Criteria
  • The patient is enrolled on COG-ACCRN07

  • The patient has a primary diagnosis of germ cell tumor (GCT) including germinoma (ICCC 9060-9065) teratoma (9080-9084), embryonal carcinoma (9070-9072), yolk sac tumor (9071),choriocarcinoma (9100, 9103, 9104), and mixed GCT (9085, 9101, 9102, 9105) in all sites including the brain and central nervous system and registered with Children's Oncology Group (COG) by a North American member institution

  • The patient must be diagnosed with a germ cell tumor between July 1, 2008 and December 31, 2015

  • The patient must be < 20 years of age at the time of diagnosis

  • The patient must have at least one biological parent alive and willing to participate

    • In the event that one case parent cannot contribute DNA, a case sibling, defined as the biological brother or sister of the study subject, may donate instead
  • All questionnaire respondents must understand English or Spanish

  • Concomitant treatment on a therapeutic trial is not required

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Correlative studiesQuestionnaire AdministrationPatients 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 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.
Correlative studiesLaboratory Biomarker AnalysisPatients 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 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.
Primary Outcome Measures
NameTimeMethod
Pediatric GCT associated with genetic susceptibilityUp to 5 years

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

Secondary Outcome Measures
NameTimeMethod
List of genes that distinguish between the three most common histologic subtypes of pediatric GCT: yolk sac tumor, teratoma, and germinomaUp 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 pyrosequencingUp 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.

Trial Locations

Locations (1)

Childrens Oncology Group

🇺🇸

Philadelphia, Pennsylvania, United States

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