Genomes of Relapsing Neuroblastoma
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REPOSITORIES: ENA
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Project description:Neuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs, but the molecular mechanisms behind this process are poorly defined. We here used whole-exome sequencing, mRNA expression, array CGH and DNA methylation analysis to holistically characterize 16 paired samples from neuroblastoma patients at diagnosis and relapse. The mutational burden significantly increased in relapsing tumors accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression. Promoter methylation patterns were consistent over disease course and patient-specific. Recurrent alterations at relapse included mutations in the putative CHD5 neuroblastoma tumor suppressor, chromosome 9p losses, DOCK8 mutations, inactivating mutations in PTPN14 and a relapse-specific activity pattern for the PTPN14 target gene, YAP. Recurrent new mutations in HRAS, KRAS, DOCK8 and genes mediating cell-cell interaction in 13/16 relapse tumors also indicate disturbances in signaling pathways mediating mesenchymal transition. Our data shed first light on genetic alteration frequency, identity and evolution in neuroblastoma.
| EGAS00001001387 | EGA
Project description:Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses, to track tumorsâ genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally-unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally-related relapses were detected: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3-p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses. There are 62 copy number Agilent 180k SurePrint arrays in total, which represent 40 cases. There are 21 arrays of primary relapsing DLBCL tumors, 21 arrys of matched relapses and 20 arrays of non relapsing DLBCLs.
2016-06-01 | E-GEOD-65720 | biostudies-arrayexpress
Project description:Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses, to track tumors’ genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally-unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally-related relapses were detected: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3-p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses.
2016-06-01 | GSE65720 | GEO
Project description:In the absence of recurrent gene mutations, evidence accumulates that epigenetic deregulation plays a prominent role in neuroblastoma biology. Here we provide genome wide H3K27ac profiles in 60 primary neuroblastoma samples.
2020-09-16 | GSE135756 | GEO
Project description:In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol.
2012-06-18 | GSE32664 | GEO
Project description:In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol. This submission contains 87 exon array profiles and are used together with exon array data from 26 Samples in GSE21713 (see 'Relation' links below) to predict the outcome of patients with neuroblastoma. The resulting dataset, which is linked below as a supplementary file ('GSE32664_complete_RMA_data.txt'), was used for the subsequent analyses.
2012-06-17 | E-GEOD-32664 | biostudies-arrayexpress
Project description:Previous studies have reported that metastatic tumor cells acquire genomic aberrations compared to those present in the primary due to an unstable genome. However, it is not clear if all malignancies follow a similar pattern. Neuroblastoma is the most common extra-cranial solid tumor of childhood. To examine how the neuroblastoma genome changes during tumor progression, we investigated chromosomal structural alterations across three tumors from a patient with hisg-risk neuroblastoma. The tumors included the primary tumor, one metastatis collected at diagnosis before any treatment, and a second metastatis collected during post mortem investigation. The recapitulated chromosomal structural alterations demonstrated that all three tumors had extensive chromosomal alterations involving virtually every chromosome. All tumors were aneuploid and shared many chromosomal alterations often seen in neuroblastoma. Despite some tumor to tumor structural variability, approximately 81-91% of the altered regions were shared among the three tumor genomes with primary tumor and pre-treamment metastatis being the most similar.
2011-12-01 | GSE33987 | GEO
Project description:Comprehensive expression profiling of disseminated neuroblastoma with favorable and unfavorable outcome using SAGE. Results provide insight into the molecular pathogenesis of spontaneous regression and progression of metastatic neuroblastoma and may be used for improving risk estimation of patients with disseminated neuroblastoma. Keywords: gene expression SAGE-based, neuroblastoma, primary tumor, disseminated disease Samples analyzed: 9 (stage 4S neuroblastoma: n=5, stage 4 neuroblastoma: n=3, neuroblastoma cell line: n=1)
2006-09-06 | E-GEOD-4991 | biostudies-arrayexpress
Project description:We performed genotyping of Neuroblastoma Primary tumors using Illumina HumanHap 550 - v1,v3,v3duo and 610 Quad genotyping beadchips.
2011-09-15 | GSE19385 | GEO