Familial Investigations of Childhood Cancer Predisposition (SJFAMILY)
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|ClinicalTrials.gov Identifier: NCT03050268|
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : May 13, 2022
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.
- 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.
- Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.
|Condition or disease|
|Acute Leukemia Adenomatous Polyposis Adrenocortical Carcinoma AML BAP1 Tumor Predisposition Syndrome Carney Complex Choroid Plexus Carcinoma Constitutional Mismatch Repair Deficiency Syndrome Diamond-Blackfan Anemia DICER1 Syndrome Dyskeratosis Congenita Emberger Syndrome Familial Acute Myeloid Leukemia Familial Adenomatous Polyposis Fanconi Anemia Familial Cancer Familial Wilms Tumor Familial Neuroblastoma GIST Hereditary Breast and Ovarian Cancer Hereditary Paraganglioma-Pheochromocytoma Syndrome Hodgkin Lymphoma Juvenile Polyposis Li-Fraumeni Syndrome Lynch Syndrome MDS Melanoma Syndrome Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia Type 2 Neuroblastoma Neurofibromatosis Type 1 Neurofibromatosis Type II Nevoid Basal Cell Carcinoma Syndrome Non Hodgkin Lymphoma Noonan Syndrome and Other Rasopathy Overgrowth Syndromes Pancreatic Cancer Peutz-Jeghers Syndrome Pheochromocytoma/Paraganglioma PTEN Hamartoma Tumor Syndrome Retinoblastoma Rhabdoid Tumor Predisposition Syndrome Rhabdomyosarcoma Rothmund-Thomson Syndrome Tuberous Sclerosis Von Hippel-Lindau Disease|
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.
|Study Type :||Observational|
|Estimated Enrollment :||3000 participants|
|Official Title:||Familial Investigations of Childhood Cancer Predisposition|
|Actual Study Start Date :||April 6, 2017|
|Estimated Primary Completion Date :||March 31, 2037|
|Estimated Study Completion Date :||March 31, 2037|
- 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.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03050268
|Contact: Kim E. Nichols, MDfirstname.lastname@example.org|
|Contact: Jamie L. Maciaszek, PhDemail@example.com|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Kim E. Nichols, MD 866-278-5833 firstname.lastname@example.org|
|Principal Investigator: Kim E. Nichols, MD|
|Principal Investigator:||Kim E. Nichols, MD||St. Jude Children's Research Hospital|