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Integrative profiling of follicular lymphoma at diagnosis and relapse

ABSTRACT: B-cells were purified from cyropreserved tumor cell suspensions by FACS, DNA isolated, and interogated using Affymetrix 250K Nsp SNP microarrays. Aim: To track the evolution of genetic alterations during progression of follicular lymphoma. One array per tumor.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Green

PROVIDER: E-GEOD-56311 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation.

Green Michael R MR Kihira Shingo S Liu Chih Long CL Nair Ramesh V RV Salari Raheleh R Gentles Andrew J AJ Irish Jonathan J Stehr Henning H Vicente-Dueñas Carolina C Romero-Camarero Isabel I Sanchez-Garcia Isidro I Plevritis Sylvia K SK Arber Daniel A DA Batzoglou Serafim S Levy Ronald R Alizadeh Ash A AA

Proceedings of the National Academy of Sciences of the United States of America 20150223 10

Follicular lymphoma (FL) is incurable with conventional therapies and has a clinical course typified by multiple relapses after therapy. These tumors are genetically characterized by B-cell leukemia/lymphoma 2 (BCL2) translocation and mutation of genes involved in chromatin modification. By analyzing purified tumor cells, we identified additional novel recurrently mutated genes and confirmed mutations of one or more chromatin modifier genes within 96% of FL tumors and two or more in 76% of tumor ...[more]

PMID: 25713363

Similar Datasets

Integrative profiling of follicular lymphoma at diagnosis and relapse

Project description:Follicular lymphoma (FL) is incurable with conventional therapies and has a clinical course typified by multiple relapses after therapy. These tumors are genetically characterized by B-cell leukemia/lymphoma 2 (BCL2) translocation and mutation of genes involved in chromatin modification. By analyzing purified tumor cells, we identified additional novel recurrently mutated genes and confirmed mutations of one or more chromatin modifier genes within 96% of FL tumors and two or more in 76% of tumors. We defined the hierarchy of somatic mutations arising during tumor evolution by analyzing the phylogenetic relationship of somatic mutations across the coding genomes of 59 sequentially acquired biopsies from 22 patients. Among all somatically mutated genes, CREBBP mutations were most significantly enriched within the earliest inferable progenitor. These mutations were associated with a signature of decreased antigen presentation characterized by reduced transcript and protein abundance of MHC class II on tumor B cells, in line with the role of CREBBP in promoting class II transactivator (CIITA)-dependent transcriptional activation of these genes. CREBBP mutant B cells stimulated less proliferation of T cells in vitro compared with wild-type B cells from the same tumor. Transcriptional signatures of tumor-infiltrating T cells were indicative of reduced proliferation, and this corresponded to decreased frequencies of tumor-infiltrating CD4 helper T cells and CD8 memory cytotoxic T cells. These observations therefore implicate CREBBP mutation as an early event in FL evolution that contributes to immune evasion via decreased antigen presentation.

2015-03-02 | GSE56311 | GEO

SNP array data for 50 leukemia remission samples

Project description:250k Sty, 250k Nsp, 250k Hind and 250k Xba Affymetrix SNP arrays for 50 leukemia remission samples used as controls for copy number analysis for GSE9109 and GSE9112. Keywords: Acute leukemia, BCR-ABL1, chronic myeloid leukemia, copy number analysis, loss-of-heterozygosity, genomics *** Due to privacy concerns, the primary SNP array data is no longer available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access using the Web links below. ***

2009-09-02 | GSE9111 | GEO

Detection of chromosomal aberrations in renal tumors by virtual karyotyping with SNP microarrays

Project description:Renal epithelial neoplasms have characteristic chromosomal imbalances that can be used for classification. We have previously shown that virtual karyotypes (v-karyotype) derived from SNP microarrays can be performed on formalin-fixed paraffin embedded (FFPE) tissue samples but a direct comparison with karyotypes obtained by conventional cytogenetics has not been done. 20 archival FFPE tumor samples were analyzed with Affymetrix 10K 2.0 or 250K Nsp SNP microarrays. 19 archival FFPE tumor samples were analyzed with Affymetrix 10K 2.0 or 250K Nsp SNP microarrays and virtual-karyotype results compared to those obtained by Cytogenetics.

2009-02-19 | E-GEOD-12808 | biostudies-arrayexpress

Detection of chromosomal aberrations in renal tumors by virtual karyotyping with SNP microarrays

2009-02-19 | GSE12808 | GEO

Virtual Karyotyping of Androgen Insensitive Prostate Cancer

Project description:We investigated chromosomal imbalances in samples from patients with androgen insensitive prostate cancer. 4 archival FFPE tumor samples were analyzed with Affymetrix 250K Nsp SNP microarrays and virtual-karyotype results for PTEN region were compared to PTEN deletion analysis by FISH.

2010-04-03 | E-GEOD-13439 | biostudies-arrayexpress

ccRCC_250K_tumor - samples

Project description:ccRCC case samples using 250K Nsp

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DBA_250K - samples

Project description:DBA case samples using 250K Nsp

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EGAD00010000484

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Analysis of the coding exome of follicular lymphoma

Project description:Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the Western world. FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and high-resolution SNP 6.0 array profiling of 12 highly purified FL cases and validation of mutations in an expansion cohort of 45 cases. In addition to confirming high-frequency mutations in MLL2, CREBBP and BCL2, we report identification of 18 recurrently mutated genes in FL. These include novel mutations in MCL1, IRF8 and POU2FA/OCT2, and high-frequency mutations in various components of the linker histone HIST1H1. Further, multiple novel mutated genes located within regions of acquired uniparental disomy (aUPD) are identified, providing candidate genes for this common lesion type in FL. In aggregate, these data substantially broaden our understanding of the types and frequency of recurrently mutated genes and pathways in FL Twelve paired normal and tumor follicular lymphoma cases were profiled by SNP array for this study. However, in addition the data from 125 CEL files derived from the DNA of flow-sorted CD3+ cells from 125 CLL patients (122 CEL files from GSE30777) were used to firmly establish a normal copy number baseline for the dChip software to compute all subsequent normal and tumor DNA copy number values.

2014-01-17 | E-GEOD-50973 | biostudies-arrayexpress

SNP array data for 36 acute myeloid and lymphoblastic leukemia cell lines

Project description:Copy number and LOH analysis was performed for 36 acute leukemia cell lines. All cases were genotyped with Affymetrix 250k Sty and Nsp arrays. Keywords: Acute leukemia, BCR-ABL1, cell lines, copy number analysis, loss-of-heterozygosity, genomics *** Due to privacy concerns, the primary SNP array data is no longer available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access using the Web links below. ***

2009-09-02 | GSE9112 | GEO

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