Rare Tumors and Cancer Predisposition in Individuals and Families

• INCLUSION CRITERIA:

Although specific familial syndromes vary in prevalence by sex, race or ethnicity, no one is excluded from participation by sex, gender, race or ethnicity. Since families participate in studies, the sex distribution is essentially balanced, and all ages are included. Minor children below the age of assent are actively studied only when the benefits of participation outweigh the risks.

Affected: An individual who meets any of the following criteria will be eligible to participate in this study:

• Personal medical history of neoplasia of an unusual type, pattern, or number; or,
• Known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation,

diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.).

• There is no age restriction; therefore including viable neonates However, children \< 3 years old will not come to the Clinical Center unless clinically indicated until they are >= 3 years old.
• Participant or their Legally Authorized Representative (LAR) must sign and date an IRB approved informed consent form (signed on paper or electronically for the Field Cohort / signed on paper for the Clinic Center Cohort)

Unaffected Controls: An individual who meets any of the following criteria will be eligible to participate in this study:

• Family medical history of neoplasia of an unusual type, pattern, or number; or,
• Known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation,

diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.).

• There is no age restriction; therefore including viable neonates. However, children \< 3 years old will not come to the Clinical Center unless clinically indicated until they are >= 3 years old.
• Participant or their LAR must sign and date an IRB-approved informed consent form (signed on paper or electronically for the Field Cohort / signed on paper for the Clinic Center Cohort)

Personal and family medical history will be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are required. The types of suspected factors predisposing to neoplasia and/or familial tumors under active accrual and study will be investigator- and hypothesis-driven. This approach permits CGB investigators to remain alert to the opportunities afforded by clusters of rare tumors in families and individuals, and to be more responsive to the dynamic research priorities in cancer genetics.

EXCLUSION CRITERIA

Affected: An individual who meets any of the following criteria will be excluded from participation in this study:

• Referred individuals for whom reported diagnoses cannot be verified
• Inability of the participant or LAR to understand and be willing to sign a written informed consent document.
• Referred individuals who are eligible for other CGB protocols that are specific to a hereditary cancer syndrome (e.g., Li-Fraumeni Syndrome, Familial Melanoma) Unaffected Controls: An individual who meets any of the following criteria will be excluded

from participation in this study:

• Referred families for whom reported diagnoses cannot be verified
• Inability of the participant or LAR to understand and be willing to sign a written informed consent document.
• Referred families who are eligible for other CGB protocols that are specific to a hereditary cancer syndrome (e.g., Li-Fraumeni Syndrome, Familial Melanoma)