MYC-negative BL frequent in posttransplant patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Julio Finalet
PROVIDER: E-GEOD-64086 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We performed genomic and transcriptomic analysis of seven cases of molecular Burkitt lymphoma (mBL) developed in immunosuppressed patients who underwent solid organ transplantation. Interestingly, three cases (43%) were MYC-translocation-negative and revealed the 11q-gain/loss aberration recently identified in 3% of mBL developed in immunocompetent hosts.1 Based on array CGH data, minimal gain and loss regions of 11q (MGR/~4Mb and MLR/~13.5Mb, respectively) were defined and integrative genomic and transcriptomic analysis identified 35 differentially expressed genes, when compared with classic BL. All 16 MGR-dysregulated genes were upregulated, including cancer related USP2, CBL and PAFAH1B2. As expected, all 19 MGL-dysregulated genes were downregulated and two of them, TBRG1 and EI24, are potential tumor suppressor genes. Interestingly, the vast majority of dysregulated 11q23-q25 genes are involved in the MYC and TP53 networks. We hypothesize that the 11q-gain/loss aberration represents a “molecular variant” of t(8q24/MYC) and affects the same pathological pathways as the MYC oncogene. Seven cases of PTLD with BL features were selected from a cohort of 174 posttransplant patients diagnosed with PTLD between 1989 and 2012 at the University Hospitals of KU Leuven (Leuven, Belgium). In addition, five classic BL cases were selected as immunocompetent controls (IC-BL). Morphologic, immunophenotypic, clinical and cytogenetic characteristics of the selected cases were reviewed.
2014-12-12 | E-GEOD-64083 | biostudies-arrayexpress
Project description:Our study provides evidence that JAK2, PDL1 and PDL2 are recurrently affected by structural and numerical aberrations in lymphoid neoplasms. The study highlights the role of PDL1/PDL2 in lymphoma progression. single case analysis
2013-04-13 | E-GEOD-46005 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-24 | E-GEOD-57944 | biostudies-arrayexpress
Project description:Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six HSTL cases with i(7)(q10) and three cases with ring 7 [r(7)], a rare variant aberration. Using high resolution array CGH, we prove that HSTL is characterized by the common loss of a 34.88 Mb region at 7p22.1p14.1 (3506316-38406226 bp) and duplication/amplification of a 38.77 Mb region at 7q22.11q31.1 (86259620-124892276 bp). Our data indicate that i(7)(q10)/r(7)-associated loss of 7p22.1p14.1 is a critical event in the development of HSTL, while gain of 7q sequences drives progression of the disease and underlies its intrinsic chemoresistance. Loss of 7p22.1p14.1 does not target a postulated tumor suppressor gene but unexpectedly enhances the expression of CHN2 from the remaining 7p allele, resulting in overexpression of β2-chimerin and dysregulation of a pathway involving RAC1 and NFATC2 with a cell proliferation response. Gain of 7q leads to increased expression of critical genes, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any additional recurrent mutations or gene fusions, suggesting that i(7)(q10) is the only driver event in this tumor. Our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies Total genomic DNA was isolated from fresh frozen lymphoma samples using standard procedures. Genomic profiling, following the manufacturer’s protocols, was performed using the Affymetrix CytoScan HD arrays (www.affymetrix.com)
2014-05-24 | E-GEOD-57943 | biostudies-arrayexpress
Project description:Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) Cytogenetics arrays; The patient’s mother was heterozygous for an inactivating mutation in CD45, while the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. Affymetrix SNP Cytogenetics arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved sorted PMBC and buccal samples. Copy number and allele analysis of Affymetrix Cytogenetics arrays was performed for the patient's and his parent's samples.
2012-02-10 | E-GEOD-35674 | biostudies-arrayexpress
Project description:We performed genomic and transcriptomic analysis of seven cases of molecular Burkitt lymphoma (mBL) developed in immunosuppressed patients who underwent solid organ transplantation. Interestingly, three cases (43%) were MYC-translocation-negative and revealed the 11q-gain/loss aberration recently identified in 3% of mBL developed in immunocompetent hosts.1 Based on array CGH data, minimal gain and loss regions of 11q (MGR/~4Mb and MLR/~13.5Mb, respectively) were defined and integrative genomic and transcriptomic analysis identified 35 differentially expressed genes, when compared with classic BL. All 16 MGR-dysregulated genes were upregulated, including cancer related USP2, CBL and PAFAH1B2. As expected, all 19 MGL-dysregulated genes were downregulated and two of them, TBRG1 and EI24, are potential tumor suppressor genes. Interestingly, the vast majority of dysregulated 11q23-q25 genes are involved in the MYC and TP53 networks. We hypothesize that the 11q-gain/loss aberration represents a M-bM-^@M-^\molecular variantM-bM-^@M-^] of t(8q24/MYC) and affects the same pathological pathways as the MYC oncogene. Seven cases of PTLD with BL features were selected from a cohort of 174 posttransplant patients diagnosed with PTLD between 1989 and 2012 at the University Hospitals of KU Leuven (Leuven, Belgium). In addition, five classic BL cases were selected as immunocompetent controls (IC-BL). Morphologic, immunophenotypic, clinical and cytogenetic characteristics of the selected cases were reviewed.
2014-12-12 | E-GEOD-64085 | biostudies-arrayexpress
Project description:Cytogenetic analysis of 36 pheochromocytoma and four paraganglioma using high density arrays A series of 36 pheochromocytoma and four paraganglioma were analysed for genomic structural alterations using high density copy number arrays
2014-09-21 | E-GEOD-61594 | biostudies-arrayexpress
Project description:Posterior amorphous corneal dystrophy (PACD) is a rare, autosomal dominant disorder affecting the cornea and iris. After next-generation sequencing of the family in which linkage analysis identified a chromosomal locus for PACD on 12q21.33 failed to yield a pathogenic mutation, array-based copy number analysis and qPCR detected a deletion on 12q21.33 containing four genes encoding small leucine-rich proteoglycans (SLRPs): KERA, LUM, DCN, and EPYC. Two other families with PACD also demonstrated deletion of these SLRPs, which together with murine models of KERA, LUM, and DCN deficiency provide convincing evidence that PACD is caused by haploinsufficiency of these SLRPs. Copy number analysis of 750K SNP and 1.9 non-polymorphic probes present on the Affymetrix CytoScan HD array. Samples were separated by affection status. Eight unaffected and 5 affected samples from across 3 families were analyzed. Analysis was performed using the Affymetrix Chromosome Analysis Suite (ChAS) v.2.0 software.
2014-06-04 | E-GEOD-50573 | biostudies-arrayexpress
Project description:Aneuploidy is among the most common hallmarks of cancer, yet the underlying genetic mechanisms are still poorly defined. We have recently identified STAG2 as a gene that is mutated in human cancer and whose inactivation leads directly to chromosomal instability and aneuploidy. However, no single tumor type has yet been identified in which inactivation of a cohesin subunit represents a predominant mutational event. Here we used immunohistochemistry to screen a panel of 2,214 tumors from each of the major human tumor types to identify additional tumor types harboring somatic loss of STAG2. Strikingly, STAG2 expression was completely absent in 18% of urothelial carcinomas, the most common type of bladder cancer and the fifth most common cancer in the United States. DNA sequencing revealed that somatic mutations of STAG2 were present in 21% of urothelial carcinomas, which were found to be a group of highly aneuploid tumors. The acquisition of STAG2 mutations was shown to be an early event in the pathogenesis of urothelial carcinoma. STAG2 loss was significantly associated with lymph node invasion, increased disease recurrence, and reduced cancer-specific survival. These results identify STAG2 as one of the most commonly mutated genes in bladder cancer discovered to date, and demonstrate that STAG2 inactivation defines an aggressive subtype of bladder cancer with particularly poor prognosis. Affymetrix CytoScan HD Arrays were performed according to the manufacturer's directions on genomic DNA extracted directly from snap-frozen human urothelial carcinoma primary tumors. Copy number analysis using Affymetrix CytoScan HD Arrays was performed for 12 human urothelial carcinomas of the bladder with truncating mutations of the STAG2 gene.
2013-06-30 | E-GEOD-41581 | biostudies-arrayexpress
Project description:Purpose: Chromosomal microarray analysis (CMA) to assess copy number variation (CNV) content is now used as a first tier genetic diagnostic test for individuals with unexplained neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA). Over 100 cytogenetic labs worldwide are using the Affymetrix CytoScan HD 2.7M array to genotype >15,000 clinical samples per month. The aim of this study is to develop a CNV resource from a population control cohort that can be used as a community resource for interpretation of clinical and research samples. Methods: We have genotyped a large population control set (1,000 individuals from our Ontario Population Genomics Platform (OPGP)) using the Affymetrix CytoScan HD microarray comprising 2.7 million probes. Four independent algorithms were applied to detect and assess high confidence CNVs. Reproducibility and validations were quantified using sample replicates and Quantitative-PCR (QPCR), respectively. Results: DNA from 873 individuals from the OPGP cohort passed quality control and we have identified 71,178 CNVs (81 CNVs/individual) distributed across 796 different cytogenetic regions in the genome; 9.8% of the CNVs were previously unreported. After applying three layers of filtering criteria, from our high confidence CNVs dataset, we obtained a >95% reproducibility and >90% validation rate. Due to the array's high probe density within genic regions, our high confidence CNV data set show 73% of the detected CNVs overlapped at least one gene. Conclusion: The genotype data and annotated CNVs presented in this study will represent a valuable public resource enabling clinical genetics research and diagnostics. For array quality control, CEL files were processed using modules from the Affymetrix power tools and genotypes were extracted from the CHP file. Samples passing the median of the absolute pairwise differences (MAPD) < 0.20 and waviness-sd < 0.11 were retained for further analysis. After multiple checks, we excluded 52 samples that do not meet quality control (QC) cutoffs. To confirm the sample's self-reported gender, we have matched the sex chromosome information from the array and identified six samples with gender mismatch, which were excluded from the analysis. We also excluded 47 samples due to excessive CNV calls. A final set of 895 samples were used for further analysis. This number included 22 sample replicates (indicated by _1 following the Sample title), which were used to determine reproducibility of the array calls. The CNV data for this study is available from dbVar (NCBI), DGVa (EBI) accession number estd212, and DGV.
2014-07-24 | E-GEOD-59150 | biostudies-arrayexpress