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Recurrent 11q aberrations in MYC-neg mature aggressive B-cell lymphomas resembling BL

ABSTRACT: Copy number analysis using Agilent 244k or 180k (Case9) arrays was performed for 8 MYC-negative B-cell lymphomas, with sex-matched control DNAs Agilent 244k (cases 4-7 and 10-12) and 180k (Case9) arrays

ORGANISM(S): Homo sapiens

SUBMITTER: Itziar Salaverria

PROVIDER: E-GEOD-47506 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Recurrent 11q aberrations in MYC-neg mature aggressive B-cell lymphomas resembling BL

Project description:Copy number analysis using Agilent 244k or 180k (Case9) arrays was performed for 8 MYC-negative B-cell lymphomas, with sex-matched control DNAs

2014-01-10 | GSE47506 | GEO

A recurrent 11q aberration pattern characterizes a subset of MYC-negative mature aggressive B-cell lymphomas resembling Burkitt lymphoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-10 | E-GEOD-47508 | biostudies-arrayexpress

Follicular lymphoma in situ and partial involvement by follicular lymphoma are clona lesions that carry the t(14;18) and lack genetic secondary alterations

Project description:Follicular lymphoma (FL) is characterized by the t(14;18)(q32;q21), frequent numerical chromosomal alterations, and recurrent somatic mutations. However, no genetic studies are available for FL in situ (FLIS), a putative precursor lesion of FL. In this study, we analyzed cases of FLIS without manifest (m)FL, partial involvement by FL (PFL), and paired cases of FLIS and mFL to detect possible early chromosomal imbalances, as well as DNA-methylation patterns of genomic regions of selected genes. We demonstrated that paired FLIS and mFL cases are always clonally related. FLIS and PFL have no or few secondary chromosomal imbalances detectable by copy number arrays and a lower level of gene methylation as compared to mFL. Additionally, EZH2 Tyr641 mutations were detected in a subset of both FLIS and PFL cases. In conclusion, this study provides evidence that FLIS represents a FL precursor lesion of long-lived clonal B-cells carrying the t(14;18) with no or few secondary genetic changes. The earliest secondary genetic alterations detected in FLIS are the EZH2 Tyr641 mutation and low levels of CNAs, as evidence of clonal evolution. Our data suggest that there may be more than one distinct lesion driving the progression from FLIS to manifest lymphoma. DNA from cases, 20 tumor samples (10 in situ Follicular lymphoma, 4 Partial infiltration folliculary lymphoma and 6 manifest FL) were analyzed with Agilent-014693 Human Genome CGH Microarray 244A platform for copy number alterations study. For cases 9-14 paired samples of in situ follicular lymphoma and manifest follicular lymphoma were analyzed. Agilent-014693 Human Genome CGH Microarray 244A arrays were performed according to the manufacturer's directions on DNA extracted from lymph nodes that were hybridized against a normal DNA (pool) of the same gender.

2013-11-12 | E-GEOD-48548 | biostudies-arrayexpress

Detection of chromothripsis-like patterns from custom array platform for chronic lymphocytic leukemia diagnosis (qchip Hemo custom array v3)

Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients. Copy number analysis using Custom Agilent 60K was performed on 47 chronic lymphocytic Leukemia patients with sex-matched control DNAs

2015-08-31 | E-GEOD-66922 | biostudies-arrayexpress

CCND2 rearrangements are the most frequent genetic events in Cyclin D1-negative mantle cell lymphoma [Agilent]

Project description:Cyclin D1-negative mantle cell lymphomas (MCL) are not well characterized, in part due to the difficulties in their recognition. SOX11 has been recently identified as a reliable biomarker of MCL, also expressed in the cyclin D1-negative variant. We investigated 40 lymphomas with MCL morphology and immunophenotype, negative for cyclin D1 expression/t(11;14)(q13;q32) but SOX11-positive. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and had a poor outcome (5-year overall survival 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18/22 cases, in particular with light chains (10 IGK@, 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2 and CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1-negative SOX11-positive MCL analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11-positive MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome to the patients. This comprehensive characterization of a large series of cyclin D1-negative MCL indicates that these tumors are clinically and biologically similar to the conventional cyclin D1-positive MCL and provides a basis for the proper identification and clinical management of these patients. Copy number analysis of Agilent 1*1M arrays was performed for 27 MCL, with sex-matched control DNAs and without duplicates or dye-swapt.

2012-12-19 | E-GEOD-42917 | biostudies-arrayexpress

CCND2 rearrangements are the most frequent genetic events in Cyclin D1-negative mantle cell lymphoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2012-12-19 | E-GEOD-42854 | biostudies-arrayexpress

Deletion of UTX, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

Project description:Kabuki syndrome (KS) is a rare multiple congenital anomalies/mental retardation (MCA/MR) syndrome described in 19811,2. In 2010, exome sequencing identified MLL2 mutations in patients with KS3. Since then, 5 studies identified a mutation in MLL2 in 56-75,6% of KS patients3-7. Here, we describe 2 KS and 1 KS-like patient with a de novo partial or complete deletion of UTX, a histone demethylase interacting with MLL2 in gene regulation. UTX locates on the X chromosome and we showed that the X chromosome with the deleted copy of UTX is preferentially inactivated despite the fact that UTX escapes X-inactivation. This study unveiled deletion of UTX as a second cause of KS and highlights the growing role of histone methylase/demethylase in MCA/MR syndrome. Two patients were analysed by Agilent array CGH 244K (AMADID: 014693) Three patients DNA were analyzed by CGH on custom targeted array 44K (AMADID: 032482). Two of them were initially analyzed using 244K Whole genome Arrays (AMADID: 014693). One third patient was selected given suspicion of deletion in one of the targeted gene (KDM6A) as amplification of some exons performed in our lab to sequence this gene failed.

2012-01-01 | E-GEOD-32567 | biostudies-arrayexpress

Human rectal adenoma (8 cases) vs. rectal carcinoma (8 cases)

Project description:Genomic profiling of human rectal adenoma and carcinoma by array-based comparative genomic hybridization Two group experiment, rectal adenoma vs. rectal carcinoma. Biological replicates: 8 adenomas vs. 8 carcinomas

2011-12-20 | E-GEOD-34472 | biostudies-arrayexpress

Desmoplastic Melanoma

Project description:High resolution aCGH was performed on 10 primary Desmoplastic Melanomas (DMs). DMs are a rare subtype of melanoma known for their pronounced desmoplastic stroma and spindled melanocytes. 10 samples were hybridized to Agilent 1 Million feature two color arrays as compared to a panel of normal male DNA. 6 samples were hybridized to Agilent 244K feature two color arrays as compared to a panel of normal male DNA. 34 samples were hybridized to Agilent 180K feature two color arrays as compared to a panel of normal male DNA.

2015-08-07 | GSE55150 | GEO

A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.

Project description:The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.

| S-EPMC3931189 | biostudies-literature

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