Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA362266 | ENA |
REPOSITORIES: ENA
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Project description:Detectable clonal mosaicism for large chromosomal events has been associated with aging and increased risk of hematological and some solid cancers. We hypothesized that genetic cancer predisposition disorders such as Fanconi anemia (FA) could manifest a high rate of chromosomal mosaic events (CMEs) in peripheral blood, which could be used as early biomarkers of cancer risk. We studied the prevalence of CMEs by Single-Nucleotide Polymorphism (SNP) array in 130 FA patients’ blood DNA and their impact on cancer risk. We detected 51 CMEs (4.4-159Mb in size) in 16/130 patients (12.3%), 9 of them with multiple CMEs. Most frequent events were gains at 3q (n=6) and 1q (n=5), both previously associated with leukemia, as well as rearrangements with breakpoint clustering within the Major Histocompatibility Complex (MHC) locus (p=7.3x10-9). Compared to 15743 age-matched population controls, FA patients had 126-140 higher risk of detectable CMEs in blood (p<2.2x10-16). Prevalent and incident hematologic and solid cancers were more common in CME carriers (OR=11.6, CI95%=3.4-39.3, p=2.8x10-5), leading to poorer prognosis. The age-adjusted hazard risk (HR) of having cancer was almost 5 times higher in FA individuals with CMEs than in those without CMEs. Regarding survival, the HR of dying was 4 times higher in FA individuals having CMEs (HR=4.0, CI95%=2.0-7.9, p=5.7x10-5). Therefore, our data suggests that molecular karyotyping with SNP arrays in easy-to-obtain blood samples could be used for better monitoring of bone marrow clonal events, cancer risk and overall survival of FA patients.
2017-02-24 | GSE93692 | GEO
Project description:Fanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha. We used gene expression microarrays to identify transcriptomal differences between bone marrow cells from normal volunteers and from children and adults with Fanconi anemia Experiment Overall Design: Fanconi anemia patients were identified using mitomycin C and/or diepoxybutane chromosomal breakage analysis. Eleven normal volunteers and 21 FA patients were studied. All FA patients with cytogenetic evidence of clonal evolution were excluded. All FA patients with acute leukemia were excluded. RNA was prepared from freshly obtained low density mononuclear cell fractions.
2009-09-18 | E-GEOD-16334 | biostudies-arrayexpress
Project description:Transcriptomic comparison of stages of clonal evolution of Fanconi anemia modeled using induced pluripotent stem cells.
2024-04-17 | GSE205844 | GEO
Project description:Modeling clonal evolution in Fanconi anemia
| PRJNA847938 | ENA
Project description:Fanconi anemia is a rare inherited hematological disorder which commonly presents with bone marrow failure, developmental abnormalities and susceptibility to cancer with high rates of prevalence in ethnic populations. The objective of this study was to identify potential genes that aid in the progression of the disease or produce its principal symptoms and to hypothesize enabling roles for certain genes that are not part of the central molecular machinery causing the disease. A total of 2 Fanconi anemia samples were collected from patients who displayed characteristic FA features. All of them gave positive results for the DNA breakage test after mitomycin C treatment. Samples were referred by Dr. Sheila Mohan of REFAIN (Registry for Fanconi anemia in India). Whole genome microarray analysis of peripheral blood from 2 patient samples and one normal individual. Sequential analysis of microarray data was carried out using gene ontology and pathway analysis to identify candidate genes.
2010-06-24 | E-GEOD-17233 | biostudies-arrayexpress
Project description:To identify the major and differential transcriptomic components of Fanconi Anemia head and neck cancer cell lines
2021-11-26 | E-MTAB-11167 | biostudies-arrayexpress
Project description:Gene expression analysis in clonal evolution of Fanconi anemia
| PRJNA869174 | ENA
Project description:Gene expression analysis in clonal evolution of Fanconi anemia
| PRJNA869175 | ENA
Project description:Fanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha. We used gene expression microarrays to identify transcriptomal differences between bone marrow cells from normal volunteers and from children and adults with Fanconi anemia
2009-09-15 | GSE16334 | GEO
Project description:The Fanconi anemia (FA) pathway is a network of proteins critical to the preservation of genomic integrity and the prevention of cancer. FA proteins safeguard the genome by regulating the cell cycle and facilitating error-free repair of DNA damage. Bi-allelic mutation of genes encoding FA pathway proteins causes the cancer predisposition syndrome Fanconi anemia (FA), which is associated with a high incidence of acute myeloid leukemia (AML). Individuals with mono-allelic mutation of a subset FA genes do not develop FA but suffer increased lifetime risk of solid and hematological malignancies. Within the general population, approximately 14% of sporadic AMLs harbor damaging mutations within the FA pathway. Our previous work demonstrated that inhibition of the mitotic kinase PLK1 induced synthetic lethality in cells deficient for FANCA, the gene most frequently lost in FA. This finding corroborates work from others that have identified synthetic lethal interactions between PLK1 and additional FA genes (FANCG, BRCA1, and BRCA2). Together, these findings suggest that FA pathway mutations may serve as biomarkers for sensitivity to PLK1 inhibitors, which have demonstrated therapeutic efficacy in an undefined subset of AML patients. Here, THP1 AML cells were generated with shControl or shFANCA and treated with 10nM volasertib for 24 h prior to kinome profiling.
2024-11-21 | PXD048057 | Pride