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

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.

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