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NCT Number: NCT03050268

Familial Investigations of Childhood Cancer Predisposition

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing.

While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition.

The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer.

PRIMARY OBJECTIVE:

* Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members.

SECONDARY OBJECTIVE:

* Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

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Key information

Conditions

Acute Leukemia AML Abnormalities, Multiple Adenocarcinoma Adenoma Adenomatous Polyposis Adenomatous Polyposis Coli Adenomatous Polyps Adnexal Diseases Adrenal Cortex Diseases Adrenal Cortex Neoplasms Adrenal Gland Diseases Adrenal Gland Neoplasms Adrenocortical Carcinoma Anemia Anemia, Aplastic Anemia, Diamond-Blackfan Anemia, Hypoplastic, Congenital Angiomatosis BAP1 Tumor Predisposition Syndrome Basal Cell Nevus Syndrome Bone Cysts Bone Diseases Bone Diseases, Developmental Bone Marrow Diseases Bone Marrow Failure Disorders Breast Diseases Breast Neoplasms Carcinoma Carcinoma, Basal Cell Cardiovascular Abnormalities Cardiovascular Diseases Carney Complex Choroid Plexus Carcinoma Ciliopathies Colonic Diseases Colorectal Neoplasms Colorectal Neoplasms, Hereditary Nonpolyposis Congenital Abnormalities Congenital Bone Marrow Failure Syndromes Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Constitutional Mismatch Repair Deficiency Syndrome Cranial Nerve Diseases Cranial Nerve Neoplasms Craniofacial Abnormalities Cysts DICER1 Syndrome DNA Repair-Deficiency Disorders Diamond-Blackfan Anemia Digestive System Diseases Digestive System Neoplasms Disease Attributes Disease Susceptibility Dyskeratosis Congenita Ear Diseases Emberger Syndrome Endocrine Gland Neoplasms Endocrine System Diseases Eye Diseases Eye Diseases, Hereditary Eye Neoplasms Familial Acute Myeloid Leukemia Familial Adenomatous Polyposis Familial Cancer Familial Neuroblastoma Familial Wilms Tumor Fanconi Anemia Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications GATA2 Deficiency GIST Gastrointestinal Diseases Gastrointestinal Neoplasms Genetic Diseases, Inborn Genetic Diseases, X-Linked Genetic Predisposition to Disease Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Hamartoma Hamartoma Syndrome, Multiple Heart Defects, Congenital Heart Diseases Heart Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Hereditary Breast and Ovarian Cancer Hereditary Breast and Ovarian Cancer Syndrome Hereditary Paraganglioma-Pheochromocytoma Syndrome Heredodegenerative Disorders, Nervous System Hodgkin Disease Hodgkin Lymphoma Hyperpigmentation Immune System Diseases Immunoproliferative Disorders Infant, Newborn, Diseases Intestinal Diseases Intestinal Neoplasms Intestinal Polyposis Jaw Cysts Jaw Diseases Juvenile Polyposis Juvenile polyposis syndrome Lentigo Li-Fraumeni Syndrome Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Lynch Syndrome MDS Malformations of Cortical Development Malformations of Cortical Development, Group I Melanoma Melanoma Syndrome Melanosis Metabolic Diseases Multiple Endocrine Neoplasia Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia Type 2 Multiple Endocrine Neoplasia Type 2a Musculoskeletal Abnormalities Musculoskeletal Diseases Myelodysplastic Syndromes Myosarcoma Myxoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Basal Cell Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Multiple Primary Neoplasms, Muscle Tissue Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplastic Syndromes, Hereditary Nerve Sheath Neoplasms Nervous System Diseases Nervous System Malformations Neurilemmoma Neuroblastoma Neurocutaneous Syndromes Neurodegenerative Diseases Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Neuroendocrine Tumors Neurofibroma Neurofibromatoses Neurofibromatosis 1 Neurofibromatosis 2 Neurofibromatosis Type 1 Neurofibromatosis Type II Neuroma Neuroma, Acoustic Neuromuscular Diseases Nevi and Melanomas Nevoid Basal Cell Carcinoma Syndrome Non Hodgkin Lymphoma Noonan Syndrome Noonan Syndrome and Other Rasopathy Nutritional and Metabolic Diseases Odontogenic Cysts Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Ovarian Diseases Ovarian Neoplasms Overgrowth Syndromes PTEN Hamartoma Tumor Syndrome Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Paraganglioma Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral Nervous System Diseases Peutz-Jeghers Syndrome Pheochromocytoma Pheochromocytoma/Paraganglioma Pigmentation Disorders Red-Cell Aplasia, Pure Retinal Diseases Retinal Neoplasms Retinoblastoma Retrocochlear Diseases Rhabdoid Tumor Predisposition Syndrome Rhabdomyosarcoma Rothmund-Thomson Syndrome Sarcoma Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin Neoplasms Skin and Connective Tissue Diseases Stomatognathic Diseases Thoracic Neoplasms Tuberous Sclerosis Turcot syndrome Urogenital Diseases Urogenital Neoplasms Vascular Diseases Vestibulocochlear Nerve Diseases Von Hippel-Lindau Disease

Sex eligibility

All sexes

Study type

Observational

Primary location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location status: Recruiting

Location contact

Kim E. Nichols, MD

CONTACT

[email protected]

888-226-4343

Kim E. Nichols, MD

PRINCIPAL_INVESTIGATOR

About this study

During the study, blood samples or other healthy tissue will be obtained from participants, as well as medical and family histories. When possible, leftover tumor samples will also be collected. If participants agree to be re-contacted in the future, they will be asked about once each year to update their health information and family history.

A blood sample will be drawn at St. Jude or at a convenient place of the participant's choice. Saliva collection will be obtained if a blood draw is not possible. For participants who are present at St. Jude, saliva collection will generally be performed only once using a saliva collection kit. However, if the first collection is not sufficient for protocol required studies, then additional saliva samples may need to be collected, for up to a total of 5 occurrences. For non St. Jude participants, or participants who do not wish or cannot come to St. Jude, saliva will be collected locally and shipped back to the St. Jude. A skin sample will be performed as a source of germline DNA from participants who have undergone an allogeneic bone marrow transplant and do not have a source of pre-transplant DNA available. A skin sample will only be obtained one time.

The biological samples will be stored in the St. Jude Biorepository. The DNA of the samples will be studied to determine if there are changes in specific genes that might explain the cancers in the participant or their family members. When available, and if consent is given by the participant, previously collected and stored leftover tumor samples, bone marrow samples or stored DNA may be analyzed.

Genetic variants of interest include: 1) mutations in known genes that may have escaped detection through prior clinical genetic testing; 2) coding mutations predicted to disrupt protein function, particularly in genes and pathways known to be associated with cancer; 3) potential mutations in regulatory regions of the genome, as predicted by epigenetic studies. In some cases, individuals with known predisposing mutations exhibit milder, more severe or atypical phenotypes. Family members who harbor a predisposing mutation but are discordant for a cancer phenotype will be selected for cellular and genetic studies. These will include DNA sequencing and possibly also creation and analysis of induce pluripotent stem cells (iPSC), transcriptome or epigenetic analysis.

All samples will be identified by a code after removal of all personal identifiable information. Samples will remain in the repository for current and future study.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown below, you may enroll regardless of the results of your clinical genetic testing.

DEFINITION OF FAMILIAR CANCER FOR THIS PROTOCOL:

In this protocol, the definition of "Familial Cancer" is met if any of the following is present:

  • An individual with a history of cancer diagnosed under 26 years of age who has at least one first, second or third degree relative with a history of cancer diagnosed under 51 years of age; OR
  • An individual who has been diagnosed with more than one cancer, at least one of which was diagnosed under 26 years of age; OR
  • An individual with a clinical or molecular diagnosis of a known cancer predisposition syndrome; OR
  • An individual with a congenital cancer diagnosed before 6 months of age; OR
  • An individual with a rare pediatric cancer or tumor diagnosed before 26 years of age

º Excluding human papilloma virus-associated cervical cancer and non-melanoma skin cancer occurring in adults.

Inclusion criteria

  • An individual who meets this protocol's definition of "Familial Cancer," as above.
  • Biologic relatives of an individual meeting this protocol's definition of "Familial Cancer," who are either affected or unaffected by cancer.

Exclusion criteria

  • An inability or unwillingness of the research participant or his/her legally authorized representative (LAR) to provide written informed consent.
  • The participant has received allogeneic bone marrow transplantation and has NO pre-transplant germline (cancer-unaffected) DNA available AND is unwilling to provide a skin sample.

Treatment and study plan

Primary outcomes

  1. Identification of novel cancer predisposing genes

    Time frame: Up to 20 years following study activation

    Probands and cancer affected and unaffected relatives from selected families will be sequenced using Whole Genome Sequencing (WGS) or possibly Whole Exome Sequencing (WES) and analyzed to identify new predisposing genetic variants that co-segregate with the tumor phenotype. Data will be analyzed using annotation and filtering strategies to identify potentially deleterious germline mutations that co-segregate with disease.

Study contacts

Contact information is provided by the study sponsor or research team.

Kim E. Nichols, MD

CONTACT

[email protected]

888-226-4343

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Registry information

Acronym: SJFAMILY

Important dates

Study start
2017
Primary completion
2037
Study completion
2037
First posted
Feb 10, 2017
Registry last updated
Jun 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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