Project description:<p><b>Background:</b> <ul> <li>A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.</li> <li>Mutations in IBMFS genes are relevant to carcinogenesis in sporadic cancers.</li> <li>Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.</li> <li>These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.</li> <li>Carriers of IBMFS gene mutations are at increased risk of cancer.</li> <li>The prototype disorder is Fanconi Anemia (FA); other IBMFS will also be studied.</li> </ul> </p> <p><b>Objectives:</b> <ul> <li>To determine the types and incidence of specific cancers in patients with an IBMFS.</li> <li>To investigate the relevance of IBMFS gene mutations in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.</li> <li>To identify risk factors for IBMFS-related cancers in addition to the primary germline mutations.</li> <li>To determine the risk of cancer in IBMFS carriers.</li> </ul> </p> <p><b>Design:</b> <ul> <li>Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory tests, review of medical records, cancer surveillance.</li> <li>Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS.</li> <li>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.</li> </ul> </p>
Project description:<p>The purpose of this study is to characterize patients with Bone Marrow Failure Syndromes (BMFS) and to track the clinical course of patients with these diseases over time. An exact and comprehensive diagnosis at presentation is essential. Due to the sporadic nature of BMFS (aplastic anemia, myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria, pure red cell aplasia, amegakaryocytic thrombocytopenic purpura and large granular lymphocyte leukemia) most diseases have not undergone systematic long-term outcome studies.</p> <p>Individual diseases, combined under the collective entity of bone marrow failure syndromes, frequently overlap and evolve from each other. The frequency of complications, associations with other diseases, and genetic factors such as allelic polymorphisms are not well studied. Some of these syndromes are likely mediated by the cellular immune system. However, while target antigens are likely to be expressed on early hematopoietic cells, their identification has been unsuccessful.</p> <p><u>Hypothesis:</u> Clinical and epidemiologic studies may, through etiologic clues and intricate laboratory testing, facilitate the understanding of the pathophysiology of BMFS and ultimately lead to implementation of better diagnostic tools and more targeted and rational therapies.</p>
Project description:To better understand the natural history of bone marrow failure syndromes, we analyzed 124 single nucleotide polymorphism arrays (SNP-A) from a comprehensively characterized cohort of 91 patients who had SNP-A for clinical evaluation of BMFS. 67 samples from 51 patients were genotyped with the Quad610, and 57 samples from 54 patients were genotyped with the Omni1-Quad. This submission includes 55 samples from 54 patients that were genotyped with Omni1-Quad. Illumina Infinium SNP-A genotyping was performed on DNA extracted from bone marrow aspirates using standard manufacturer's protocol
Project description:To better understand the natural history of bone marrow failure syndromes, we analyzed 124 single nucleotide polymorphism arrays (SNP-A) from a comprehensively characterized cohort of 91 patients who had SNP-A for clinical evaluation of BMFS. 67 samples from 51 patients were genotyped with the Quad610, and 57 samples from 54 patients were genotyped with the Omni1-Quad. This submission includes 67 samples from 51 patients that were genotyped with Illumina Quad610 Beadchip. Illumina Infinium SNP-A genotyping was performed on DNA extracted from bone marrow aspirates using standard manufacturer's protocol