Genome-wide profiling of copy-number alteration in monoclonal gammopathy of undetermined significance
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE77975 | GEO | 2016/02/18
SECONDARY ACCESSION(S): PRJNA312349
REPOSITORIES: GEO
Similar Datasets
Project description:To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high resolution single nucleotide polymorphism (SNP) mapping array analysis in 114 samples alongside 258 samples analysed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) in order to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8q (25%), 12 (22%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%) and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescent in situ hybridisation (FISH) and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes which have functions relevant to myeloma biology. Taken together, the dysregulated genes from the myeloma genome indicate that the crucial pathways in myeloma pathogenesis include the NF-?B pathway, apoptosis, cell-cycle regulation and Wnt signalling.
2010-10-18 | GSE21349 | GEO
Project description:To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high resolution single nucleotide polymorphism (SNP) mapping array analysis in 114 samples alongside 258 samples analysed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) in order to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8q (25%), 12 (22%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%) and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescent in situ hybridisation (FISH) and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes which have functions relevant to myeloma biology. Taken together, the dysregulated genes from the myeloma genome indicate that the crucial pathways in myeloma pathogenesis include the NF-?B pathway, apoptosis, cell-cycle regulation and Wnt signalling. SNP data: 114 tumour samples (MM) analyzed by Affymetrix 500K array set (Nsp+Sty), of which 80 samples have matched peripheral blood (PB) (non-tumour) DNA performed on the same array types. Matched tumour and non-tumour samples have the same ID number, e.g. MM400 and PB400 Expression data: 258 expression samples from CD138+ cell selection
2010-11-02 | E-GEOD-21349 | biostudies-arrayexpress
Project description:Primary plasma cell leukaemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinguished from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Here, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequently altered regions were located at 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%) and 17p (35%). A relevant finding of our study was the identification of a minimal biallelical deletion (1.5 Mb) in 8p21.2 encompassing the putative tumor suppressor gene PPP2R2A that was significantly down-regulated in deleted cases. Mutations of TP53 were identified in 4 cases all but one associated with a monoallelic deletion of the gene, whereas activating mutations of BRAF occurred in one case and were absent for N- and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferases activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to our understanding of this particular form of plasma cell dyscrasia and to better elucidate the mechanisms of tumor progression in MM.
2012-10-12 | GSE39381 | GEO
Project description:Primary plasma cell leukaemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinguished from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Here, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequently altered regions were located at 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%) and 17p (35%). A relevant finding of our study was the identification of a minimal biallelical deletion (1.5 Mb) in 8p21.2 encompassing the putative tumor suppressor gene PPP2R2A that was significantly down-regulated in deleted cases. Mutations of TP53 were identified in 4 cases all but one associated with a monoallelic deletion of the gene, whereas activating mutations of BRAF occurred in one case and were absent for N- and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferases activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to our understanding of this particular form of plasma cell dyscrasia and to better elucidate the mechanisms of tumor progression in MM.
2012-10-12 | GSE39380 | GEO
Project description:Purpose: To improve clinical outcome of gastric cancer patients, most emphasis is on improving therapeutic regimens, including more extensive surgery as well as (neo)adjuvant chemotherapy. The present study set out to identify, based on DNA copy number profiling, subgroups of patients with different clinical outcomes who thus would qualify for different therapy intensities. Experimental Design: DNA of 206 gastric cancer patients was isolated and analyzed by genome wide array comparative genomic hybridization. DNA copy number profiles were evaluated and correlated to lymph node status and survival. In addition, HSP90 protein expression was analyzed and correlated to survival in 290 gastric cancer patients. Results: Frequent (>20%) DNA copy number gains were observed on chromosomes 1p, 6p, 7p, 7q, 8q, 11q, 12q, 13q, 16p, 16q, 17q, 19p, 19q, 20p, 20q, 21q and 22q, and losses on chromosomes 4p, 4q, 6p, 6q, 9p, 13q and 21q. Lymph node negative gastric cancers showed significantly more losses on chromosomes 5q11.2-q35.1, 10q11.23-21.3 and 14q32.11-q32.33. In addition, losses on 5q11.2-q31.3 and 14q32.11-q32.33 were highly correlated to good clinical outcome, in both lymph node negative and positive gastric cancer patients. Loss of expression of HSP90, located on chromosome 14q32.2, correlated to good survival time. Conclusion: Genome wide DNA copy number profiling allows to identify a subgroup of gastric cancers, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 that have an excellent clinical outcome after surgery alone, and patients with these tumors are unlikely to benefit from additional intensified therapies. Possible biological mechanisms could involve loss of heat shock proteins, of which the coding genes are located at these chromosomal regions. 183 gastric adenocarcinomas
2012-05-09 | E-GEOD-26389 | biostudies-arrayexpress
Project description:Purpose: To improve clinical outcome of gastric cancer patients, most emphasis is on improving therapeutic regimens, including more extensive surgery as well as (neo)adjuvant chemotherapy. The present study set out to identify, based on DNA copy number profiling, subgroups of patients with different clinical outcomes who thus would qualify for different therapy intensities. Experimental Design: DNA of 206 gastric cancer patients was isolated and analyzed by genome wide array comparative genomic hybridization. DNA copy number profiles were evaluated and correlated to lymph node status and survival. In addition, HSP90 protein expression was analyzed and correlated to survival in 290 gastric cancer patients. Results: Frequent (>20%) DNA copy number gains were observed on chromosomes 1p, 6p, 7p, 7q, 8q, 11q, 12q, 13q, 16p, 16q, 17q, 19p, 19q, 20p, 20q, 21q and 22q, and losses on chromosomes 4p, 4q, 6p, 6q, 9p, 13q and 21q. Lymph node negative gastric cancers showed significantly more losses on chromosomes 5q11.2-q35.1, 10q11.23-21.3 and 14q32.11-q32.33. In addition, losses on 5q11.2-q31.3 and 14q32.11-q32.33 were highly correlated to good clinical outcome, in both lymph node negative and positive gastric cancer patients. Loss of expression of HSP90, located on chromosome 14q32.2, correlated to good survival time. Conclusion: Genome wide DNA copy number profiling allows to identify a subgroup of gastric cancers, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 that have an excellent clinical outcome after surgery alone, and patients with these tumors are unlikely to benefit from additional intensified therapies. Possible biological mechanisms could involve loss of heat shock proteins, of which the coding genes are located at these chromosomal regions.
2012-05-10 | GSE26389 | GEO
Project description:Mantle cell lymphoma (MCL) is a lymphoma characterized by aberrant activation of CCND1/cyclin D1 followed by sequential genetic abnormalities. Genomic abnormalities in MCL have been extensively examined by classical cytogenetics and microarray-based comparative genomic hybridization techniques, pointing out a number of alterations in genomic regions that correlate with the neoplastic phenotype and survival. Recently, single nucleotide polymorphism genomic microarrays (SNP-chip) have been developed and used for analysis of cancer genomics. This technique allows detection of genomic changes with higher resolution, including loss of heterozygosity without changes of gene dosage, so-called acquired uniparental disomy (aUPD). As a result of the analysis, known alterations were confirmed by SNP arrays, including deletion of INK4A/ARF, duplication/amplification of MYC, deletion of ATM, and deletion of TP53. We also identified a duplication/amplification that occurred at 13q involving oncogenic microRNA, miR17-92. We found other genomic abnormalities, including duplication/amplification of cyclin D1, del(1p), del(6q), dup(3q) and dup(18q). Our SNP-chip analysis detected these abnormalities at high resolution, allowing us to narrow the size of the commonly deleted regions, including 1p and 6q. Our SNP-chip analysis detected a number of aUPD sites, including whole chromosome 9 aUPD and 9p aUPD. We also found an MCL case with 19p, leading to homozygous deletion of TNFSF genes. keyword: SNP-chip; Kawmata_MCL
2009-11-13 | GSE18820 | GEO
Project description:Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients. Single nucleotide polymorphism (SNP)-arrays allow simultaneous detection of copy-number aberrations (CNAs) and copy-number neutral loss-of-heterozygosity (CNN-LOH). In this study we investigated the presence of CNAs and CNN-LOH in newly diagnosed CLL samples from a Swedish chronic lymphocytic leukemia (CLL) cohort. In this study we could detect the known recurrent aberrations in CLL (i.e. deletions of 13q, 11q, 17p and trisomy 12). We also detected other both large and small CNAs which were mostly non-recurrent. CNN-LOH was detected on chromosome 13q in patients that carried homozygous deletion of 13q.
2009-11-23 | GSE16406 | GEO
Project description:Multiple myeloma (MM) and its premalignant precursor MGUS (monoclonal gammopathy of undetermined significance) are clonal plasma cell diseases that develop in the bone marrow (BM) and are dependent on microenvironmental interactions. Primary bone marrow stromal cells (BMSCs) are key players in the BM microenvironment, however, their role in MGUS/MM pathophysiology is not known. We therefore investigated potential disease-specific alterations in prospectively isolated BMSCs from MM, MGUS and healthy controls. Clear disease-related BMSC surface marker and gene expression differences were recorded, and deep sequencing identified shared MGUS/MM as well as MM-specific molecular signatures. Moreover, we identified genes that were deregulated in a disease-stage manner, thus reflecting the progression from normal to MGUS and MM. Analysis of primary BMSCs revealed disease-stage related protein and gene expression patterns, which provides novel insight into the stromal transitions and their functional implications for plasma cell disease development and progression.
2024-01-31 | GSE129801 | GEO
Project description:MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including lymphoma. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is poorly understood. We therefore elucidated the complete miRNome of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls. Unsupervised cluster analysis revealed that MM samples have a distinct microRNA expression profile. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell lymphomas revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in >85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis. In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease. Plasma cells (CD138+) cells were purified from bone marrow samples of 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls.
2010-09-29 | E-GEOD-24371 | biostudies-arrayexpress