Symptoms and General Pathology

All Conditions

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Syndrome

Anemia

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Fanconi Syndrome

Fanconi Anemia

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Infant, Newborn, Diseases

Aplastic Anemia

Congenital Aplastic Anemia

Diamond-Blackfan Anemia

Pure Red Cell Aplasia

Multiple Symmetric Lipomatosis

All families with a member who has one of the relevant syndromes.

NCI Family Study Referrals

Neelam Giri, M.D.

Background:

A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers.

Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.

These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.

Carriers of IBMFS pathogenic variant(s) are at increased risk of cancer.

The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied.

Objectives:

To determine the types and incidence of specific cancers in patients with an IBMFS.

To investigate the relevance of IBMFS pathogenic variant(s) in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.

To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s).

To determine the risk of cancer in IBMFS carriers.

Eligibility:

North American families with a proband with an IBMFS.

IBMFS suspected by phenotype, confirmed by pathogenic variant(s) in an IBMFS gene, or by clinical diagnostic test.

Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result.

Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase.

Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure.

Shwachman-Diamond Syndrome: malabsorption; neutropenia.

Amegakaryocytic thrombocytopenia: early onset thrombocytopenia.

Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia.

Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest.

Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts.

Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia.

First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children.

Grandparents of IBMFS-affected subjects.

Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV).

Design:

Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance.

Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS.

Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones....

Study Description:

This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of medical records, cancer surveillance. A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers.

This study will determine whether patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.

These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.

Carriers of IBMFS gene pathogenic variant(s) are at increased risk of cancer.

The prototype disorder is Fanconi Anemia (FA); other IBMFS will also be studied.

Objectives:

To determine the types and incidence of specific cancers in patients with an IBMFS.

To investigate the relevance of IBMFS gene pathogenic variants in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.

To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s).

To determine the risk of cancer in IBMFS carriers.

Endpoints:

Primary Endpoint:

-All cancers, solid tumors, and cancers specific to each type of IBMFS.

Secondary Endpints:

-Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones.

Cancer in Inherited Bone Marrow Failure Syndromes

Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study

Establish a cohort of families with IBMFS

Compare biology of IBMFS patients with general populations

Identify differences between patients with IBMFS who develop cancer and those who don't

Determine risk of cancer in IBMFS patients with specific gene mutations

National Cancer Institute (NCI)

Respiratory Tract (Lung and Bronchial) Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Disease Attributes

Malignant Mesothelioma

BAP1 Tumor Predisposition Syndrome

Individuals with history of cancer and detected or suspected germline mutation in BAP1 TPDS

First- or second-degree relatives of a cancer patient (with or without cancer) with documented BAP1 tumor predisposition syndrome (TPDS)

Deneise Francis, R.N.

David S Schrump, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

A germline mutation is a change to a person s genes that is carried through their DNA. These mutations can be passed on from parents to their offspring. Germline mutations in a gene called BAP1 are linked to the development of mesothelioma and other cancers. Researchers want to follow people with these mutations to learn more.

Objective:

To see if researchers can improve how people who have or are suspected to have a BAP1 mutation are monitored over time.

Eligibility:

People age 30 and older who are suspected to have a BAP1 germline mutation.

Design:

Participants will be screened with a personal and family medical history. Their medical records may be reviewed. They will give a blood or saliva sample to test for a BAP1 mutation. They will get genetic counseling.

To take part in this study, participants will enroll on 2 to 3 other protocols.

Participants will have a physical exam. They may have a tumor biopsy. They will give blood and urine samples. They will have skin and eye exams.

Some participants will have video-assisted thoracoscopy to examine the chest and lungs and diagnose suspicious areas. For this, a small camera is inserted into the chest through a small incision.

Some participants will have laparoscopy to examine the organs inside the abdomen. For this, a small camera is inserted into the abdomen through a small incision.

Participants will have imaging scans of the chest, abdomen, and pelvis. They may have brain scans.

Participants will visit the NIH once a year for follow-up exams.

Participation lasts indefinitely.

Background:

* Mutations involving BRCA1-Associated Protein-1 (BAP1), a nuclear deubiquitinase involved in epigenetic regulation of gene expression, DNA repair, and cellular energetics, have emerged as one of the most common somatic mutations in malignant mesotheliomas.
* Germline mutations involving BAP1 predispose individuals to mesothelioma as well as a variety of other malignancies including melanoma and lung, renal, gastric, breast, and biliary tract cancers.
* The cancer penetrance of germline BAP1 mutations is nearly 100%, with most patients developing multiple neoplasms.
* Presently there are no established guidelines for surveillance of cancer patients with germline BAP1 mutations or of cancer-free individuals with germline BAP1 mutations.

Objectives:

To prospectively gather information related to the use of dual energy computed tomographic imaging (DECT), together with minimally invasive surgical surveillance for early detection of pleural or peritoneal mesothelioma in patients with BAP1 tumor predisposition syndrome (TPDS)

Eligibility:

* Individuals with a history of any malignancy with known or suspected germline mutation involving BAP1.
* First- or second-degree relatives of patients with documented germline BAP1 mutations, who are also found to carry similar germline mutations.
* Age greater than or equal to 30

Design:

* Individuals with suspected hereditary tumor predisposition syndromes will undergo germline evaluation using CLIA-certified next-gen sequencing (NGS).
* First- and second-degree relatives of patients with germline BAP1 mutations will be offered similar NGS evaluation.
* Subjects with germline mutations in BAP1, will undergo periodic dual energy CT (DECT) scans of the chest, abdomen, and pelvis. Plasma cell-free DNA (cfDNA) will be assessed at similar intervals, and minimally invasive surveillance procedures (i.e., video- assisted thoracoscopy and laparoscopy) will be performed periodically to detect early, subclinical malignancies that may be amenable to potentially curative local interventions.

Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Documentation of the counts, incidence, and frequencies of cancers from dual energy computed tomographic imaging and minimally invasive surveillance results will be analyzed for statistical analysis for the early detection of mesotheliomas in patients with BAP1 TPDS.

Characterization of the epigenetic features of mesotheliomas associated with germline mutations in BAP1.

Tumor tissue, blood, saliva, or buccal swab specimen for genetic analyses including WES, FACS, Western blots, and RNA sequencing.

Immune System Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Genetic Predisposition to Disease

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

John T. Sandlund, MD

Familial aggregation is well recognized in some cancers. Though a number of familial cancer predisposition syndromes have been described, the nature of inherited genetic alterations in patients with a strong history of familial cancer is currently unknown, as is the case with childhood acute lymphoblastic leukemia (ALL).

The investigators are seeking to learn more about what causes leukemia and why some people and families may be at a higher risk of developing this disease. By understanding the origin of the disease, better treatments may be identified for patients with leukemia.

PRIMARY OBJECTIVE: To identify variants in genes that are inherited, have altered gene structure and/or function, and influence the risk of developing acute lymphoblastic leukemia (ALL) and other cancers.

SECONDARY OBJECTIVE: To collect demographic, clinical and laboratory information including detailed family cancer history and response of cancers to therapy for correlation with the primary objective.

This study entails clinical interviews, submission of a peripheral germline blood sample for non-tumor DNA and permission to perform biologic studies on previously stored tumor tissue if applicable and available. Participants diagnosed with cancer at outside institutions will be requested to sign a release form to allow the outside institution to send germline and/or tumor tissue to St Jude if available. For patients who have undergone a stem cell transplant, a buccal swab or saliva sample will be requested (for germline DNA). For patients with active leukemia, non-tumor cells (for germline DNA) may be obtained using a remission blood sample, a skin biopsy (to obtain fibroblasts) or may be purified by fluorescence activated cell sorting of leukemia samples. The skin biopsy will be obtained in participants 18 years of age and older. In participants less than 18 years, the skin biopsy will be accessed only if it was already collected as part of another research protocol or for clinical care.

All patients being considered for enrollment will have a clinical genetics consult by one of the study team members at which time a family history will be taken and information about genomic testing will be introduced. Detailed medical history will be obtained which includes but is not limited to demographics, clinical data including laboratory results, cancer history/diagnosis, treatment outcomes, environmental exposures and cancer risk factors to enable phenotype/genotype correlations.

Genetic Study of Familial Acute Lymphoblastic Leukemia

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.

St. Jude Children's Research Hospital

Hematologic Neoplasms

This pediatric oncology study proposing a global approach integrating trio-based whole exome sequencing, somatic DNA and RNA analysis will improve the recognition of genetic predisposition and the characterization of target therapies in children with cancer.

Exome sequencing in pediatrics cancers

Pascal Pujol, PU-PH

Background. Cancer is the leading cause of death by disease in children. Most pediatric tumors differ from adult tumors in terms of biological and clinical characteristics. In children, the part of genetic determinism could be higher since the role of environmental factors may be less pronounced than in adults and that a young age at onset is a main feature of genetic cancer predisposition. Recent studies suggested that a number of genetic predisposition remains to be characterized.

Methods. Trio-Based whole exome sequencing of germline DNA from patients (children and adults diagnosed with cancers between 0 and 17 years) and parents will be performed prospectively in a multicentric study including 40 unselected cases of malignant tumor. Participating hospitals will include the CHU of Montpellier, the CHU de Nice and the AP-HP. Tumor analysis will include whole exome analysis and transcriptome for the identification of therapeutic target and contribute to confirm potential link between constitutive mutations and tumor phenotype (such as loss of expression, loss of heterozygosity).

Perspectives. This pediatric oncology study proposing a global approach integrating trio-based whole exome sequencing, somatic DNA and RNA analysis will improve the recognition of genetic predisposition and the characterization of target therapies in children with cancer.

Analyse of Tumour and Constitutional DNA for the Study of the Determinism in Child Neoplasia

A blood sample will be taken from patients and their parents in order to carry out genetic analyses.

New generation NGS Exome sequencing in trio (patient and 2 healthy parents) on an Illumina HiSeq 2000 platform using the SureSelectXT Human All Exon 50Mb, V5 kit.

Bioinformatics analysis of the data. Confirmation of mutations by Sanger sequencing (gold standard).

In case of identification of mutations in candidate genes confirmed by Sanger sequencing, we will perform functional and clinical-genetic studies.

Soroptimist association of Monaco

University Hospital, Montpellier

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cancer in Inherited Bone Marrow Failure Syndromes	NCT00027274	Diamond Blackfa... Dyskeratosis Co... Fanconi Anemia Shwachman Diamo... Inherited Bone ...		-	National Institutes of Health Clinical Center (CC)
Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome	NCT04431024	Familial Cancer BRCA1-Associate... Tumor Predispos... Mesothelioma		30 Years -	National Institutes of Health Clinical Center (CC)
Genetic Study of Familial Acute Lymphoblastic Leukemia	NCT03067584	Acute Lymphobla...		-	St. Jude Children's Research Hospital
Analyse of Tumour and Constitutional DNA for the Study of the Determinism in Child Neoplasia	NCT04471961	Pediatric Tumor Familial Cancer Solid Tumor, Ch... Hematological T...	Exome sequencin...	-	University Hospital, Montpellier

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