INTEGRATIVE ANALYSIS OF DNA COPY NUMBER, DNA METHYLATION AND GENE EXPRESSION IN MULTIPLE MYELOMA REVEALS ALTERATIONS RELATED TO RELAPSE.
(Abstract release date: 05/19/16)
EHA Library. Krzeminski P. 06/09/16; 132803; E1254
Dr. Patryk Krzeminski
Contributions
Contributions
Abstract
Abstract: E1254
Type: Eposter Presentation
Background
Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated.
Aims
To investigate the genomic changes generated in the transition of myeloma cells from diagnosis to relapse, analyzing DNA imbalances, methylation, and transcriptomic modifications.
Methods
Twenty patients with symptomatic newly diagnosed MM were included in the study. Paired bone marrow (BM) samples were obtained at diagnosis and relapse in all the patients. A CD138 positive PC isolation using the AutoMACs automated separation system was carried out in all the BM samples (purity was above 90%). Genome-wide detection of CNA was carried out using the standard Affymetrix CytoScan 750k assay protocol (Affymetrix); DNA methylation was assessed using the “Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array” according to standard procedures by NimbleGen Systems, and gene expression profiling was performed by means of the Human Gene 1.0 ST Array (Affymetrix).
Results
Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA.
Conclusion
Cross-platform integration of three different microarrays data revealed that genomic heterogeneity of MM already described at diagnosis is subject to change at relapse, both at the DNA and RNA level. This study, also, showed a limited effect of DNA methylation changes observed at relapse on the transcriptome of myeloma cells.
Session topic: E-poster
Keyword(s): Expression profiling, Methylation, Microarray analysis, SNP
Type: Eposter Presentation
Background
Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated.
Aims
To investigate the genomic changes generated in the transition of myeloma cells from diagnosis to relapse, analyzing DNA imbalances, methylation, and transcriptomic modifications.
Methods
Twenty patients with symptomatic newly diagnosed MM were included in the study. Paired bone marrow (BM) samples were obtained at diagnosis and relapse in all the patients. A CD138 positive PC isolation using the AutoMACs automated separation system was carried out in all the BM samples (purity was above 90%). Genome-wide detection of CNA was carried out using the standard Affymetrix CytoScan 750k assay protocol (Affymetrix); DNA methylation was assessed using the “Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array” according to standard procedures by NimbleGen Systems, and gene expression profiling was performed by means of the Human Gene 1.0 ST Array (Affymetrix).
Results
Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA.
Conclusion
Cross-platform integration of three different microarrays data revealed that genomic heterogeneity of MM already described at diagnosis is subject to change at relapse, both at the DNA and RNA level. This study, also, showed a limited effect of DNA methylation changes observed at relapse on the transcriptome of myeloma cells.
Session topic: E-poster
Keyword(s): Expression profiling, Methylation, Microarray analysis, SNP
Abstract: E1254
Type: Eposter Presentation
Background
Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated.
Aims
To investigate the genomic changes generated in the transition of myeloma cells from diagnosis to relapse, analyzing DNA imbalances, methylation, and transcriptomic modifications.
Methods
Twenty patients with symptomatic newly diagnosed MM were included in the study. Paired bone marrow (BM) samples were obtained at diagnosis and relapse in all the patients. A CD138 positive PC isolation using the AutoMACs automated separation system was carried out in all the BM samples (purity was above 90%). Genome-wide detection of CNA was carried out using the standard Affymetrix CytoScan 750k assay protocol (Affymetrix); DNA methylation was assessed using the “Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array” according to standard procedures by NimbleGen Systems, and gene expression profiling was performed by means of the Human Gene 1.0 ST Array (Affymetrix).
Results
Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA.
Conclusion
Cross-platform integration of three different microarrays data revealed that genomic heterogeneity of MM already described at diagnosis is subject to change at relapse, both at the DNA and RNA level. This study, also, showed a limited effect of DNA methylation changes observed at relapse on the transcriptome of myeloma cells.
Session topic: E-poster
Keyword(s): Expression profiling, Methylation, Microarray analysis, SNP
Type: Eposter Presentation
Background
Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated.
Aims
To investigate the genomic changes generated in the transition of myeloma cells from diagnosis to relapse, analyzing DNA imbalances, methylation, and transcriptomic modifications.
Methods
Twenty patients with symptomatic newly diagnosed MM were included in the study. Paired bone marrow (BM) samples were obtained at diagnosis and relapse in all the patients. A CD138 positive PC isolation using the AutoMACs automated separation system was carried out in all the BM samples (purity was above 90%). Genome-wide detection of CNA was carried out using the standard Affymetrix CytoScan 750k assay protocol (Affymetrix); DNA methylation was assessed using the “Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array” according to standard procedures by NimbleGen Systems, and gene expression profiling was performed by means of the Human Gene 1.0 ST Array (Affymetrix).
Results
Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA.
Conclusion
Cross-platform integration of three different microarrays data revealed that genomic heterogeneity of MM already described at diagnosis is subject to change at relapse, both at the DNA and RNA level. This study, also, showed a limited effect of DNA methylation changes observed at relapse on the transcriptome of myeloma cells.
Session topic: E-poster
Keyword(s): Expression profiling, Methylation, Microarray analysis, SNP
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