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Affymetrix SNP array data for Monoclonal Gammopathies samples (2.6GB)

Genetic events mediating transformation from the pre-malignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to the late stages we performed high resolution analysis on purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high density 6.0 SNP-array. Collaborators: Lucia Lopez Corral and Maria Eugenia Sarasquete

Affymetrix SNP array data  (2.6GB) Affy SNP  (Published) 

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Sample Annotation  (9.7KB) Sample annotation  (Published) 

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Arkansas dataset (215.6MB)

Publication: Zhan F, et al. (2006) "The molecular classification of myeloma." Blood 108: 2020-8.
Principal Investigator: John D Shaughnessy, Jr.
Institution: Arkansas Cancer Research Center
Description: Gene expression data. Samples from patients with previously untreated multiple myeloma.

Gene expression data  (215.6MB) Gene expression  (Published) 

RNA of CD138-selected plasma cells from the bone marrow of 414 previously untreated patients with multiple myeloma, subsequently treated with Total Therapy 2 and Total Therapy 3, hybridized to Affymetrix U133 Plus 2.0 arrays. Normalization is MAS5. Also available from GEO (accession GSE4581).

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Sample annotation  (15.3KB) Sample annotation  (Published) 

Sample annotations, including survival data and classification as determined in the study.

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Carrasco et al. 2006 (84.3MB)

Publications: Carrasco DR, Tonon G, et al. (2006) "High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients." Cancer Cell 9: 313-25.
Principal Investigator: Ron DePinho
Institution: Dana Farber Cancer Institute, Boston (MA)
Description: Matched copy number and gene expression data. Samples from patients with previously untreated multiple myeloma.

Gene expression data  (64.0MB) Gene expression  (Published) 

RNA from CD138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy, hybridized to Affymetrix U133 Plus 2.0 expression arrays. Data is MAS5 normalized and available as a .res file. Also available from GEO (accession GSE4452).

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Copy number data  (20.3MB) Agilent aCGH  (Published) 

DNA from CD138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients hybridized to Agilent 22K comparative genomic hybridization arrays (aCGH). Per probe and segmented copy number available, both as .cn files. Also available from http://genomic.dfci.harvard.edu/.

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Patient sample annotation  (4.2KB) Sample annotation  (Published) 

Patient sample annotation, including demographics and survival data.

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Mayo Clinic Amyloid Project (204.8MB)

Publications: "Biological and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2." Blood (submitted)
Principal Investigator: Diane Jelinek
Institution: Mayo Clinic, Scottsdale (AZ)
Description: Matched gene expression profiling and array based CGH analysis of two patient samples from a myeloma patient with amyloidoisis at different clinical stages and two cell lines, ALMC-1 and ALMC-2, that were derived from these two samples.

Expression data  (20.7MB) Gene expression  (Published) 

RNA was obtained from plasma cells from bone marrow samples of a patient with primary amyloidosis at diagnosis and following a peripheral stem cell transplant. Cell lines were derived from these samples and RNA obtained. The RNA was hybridized to Affymetrix U133 Plus 2.0 expression arrays.

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Copy number data  (184.1MB) Agilent aCGH  (Published) 

DNA was obtained from plasma cells from bone marrow samples of a patient with primary amyloidosis at diagnosis and following a peripheral stem cell transplant. Cell lines were derived from these samples and DNA obtained. The DNA was hybridized to Agilent 244K aCGH arrays.

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Mayo Clinic Cell Line Dataset (457.0MB)

Publications: Keats J, et al. (2007) "Promiscuous Mutations Activate the Noncanonical NF-kappaB Pathway in Multiple Myeloma" Cancer Cell 12:131-44.
Principal Investigator: Leif Bergsagel, Michael Kuehl, John Shaughnessy Jr.
Institution: Mayo Clinic, Scottsdale (AZ)
Description: Copy number data generated by Michael Barrett at Agilent. Samples from multiple myeloma cell lines.

Cell line expression profiles  (433.4MB) Gene expression  (Published) 

RNA from various multiple myeloma cell lines was hybridized to Affymetrix U133A microarrays. Data available as raw data (zipped .cel files) or RMA normalized (.res file).

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Cell line copy number data  (23.6MB) Agilent aCGH  (Published) 

DNA from various multiple myeloma cell lines was hybridized to Agilent 44k comparative genomic hybridization arrays (aCGH).

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Mayo Clinic Patient Dataset (643.7MB)

Publications: Keats J, et al. (2007) "Promiscuous Mutations Activate the Noncanonical NF-kappaB Pathway in Multiple Myeloma" Cancer Cell 12:131-44.
Principal Investigator: Leif Bergsagel, Michael Kuehl
Institution: Mayo Clinic, Scottsdale (AZ), Arkansas Cancer Research Center
Description: Copy number data generated at the Mayo clinic and matched expression profiles generated at Arkansas Cancer Research Center. Samples from patients with multiple myeloma at different stages.

Patient sample expression profiles  (612.4MB) Gene expression  (Published) 

RNA from CD138+ plasma cells from the bone marrow of patients with MGUS, smouldering myeloma, new myeloma, or relapsed myeloma, was hybridized to Affymetrix U133A microarrays. Data available as raw data (zipped .cel files) or RMA normalized (.res file). Also available from GEO (GSE6477).

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Patient sample copy number data  (31.3MB) Agilent aCGH  (Published) 

DNA from CD138+ plasma cells from the bone marrow of patients with MGUS, smouldering myeloma, new myeloma, or relapsed myeloma, was hybridized to Agilent 44k comparative genomic hybridization arrays (aCGH).

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Patient sample annotation  (10.8KB) Sample annotation  (Published) 

Disease (multiple myeloma or MGUS), status (new, smouldering, relapsed), whether hyperdiploid, and whether chromosome 13 is deleted.

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Millennium Pharmaceuticals dataset (104.8MB)

Publication: Mulligan G, et al. (2007) "Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib." Blood 109: 3177-88.
Principal Investigator: Barbara Bryant
Institute: Millennium Pharmaceuticals
Description: Gene expression data from patients with relapsed multiple myeloma entered into phase II and III bortezomib trials

Gene expression  (104.8MB) Gene expression  (Published) 

Purified myeloma samples were collected prior to enrolment in clinical trials of bortezomib (PS-341). Samples were subject to replicate gene expression profiling using the Affymetrix 133A/B microarray. Data was normalized in MAS5.0 and the median of replicates is reported.

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MM HMCL69 Cell Line Characterization (119.0MB)

This project is funded by the Multiple Myeloma Research Foundation. The primary goal is to characterize the commercially available model systems using comparable methods to those used to characterize the panel of patient samples studied in the Multiple Myeloma Genomics Initiative. This data is mirrored from https://sites.google.com/site/jonathankeatslab/data-repository.

mRNASeq Gene Expression  (114.0MB) Gene expression  (In process) 

Gene expression levels of each cell line as measured from mRNAseq data

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Mutations  (3.9MB) Undefined  (In process) 

This excel file contains all the preliminary mutations we have identified in 69 cell lines tested to date. This is Agilent SureSelect V4+UTR exome captures, aligned with BWA, realigned, recalibrated, duplicates removed, and variants called by samtools. Any variant in 1000G, or NHLBI has been removed. Variants in dbSNP were removed unless the same variant exists in Cosmic.

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Copy Number  (1.1MB) Agilent aCGH  (In process) 

The encoded positions are GRCh37/hg19. The copy number values are smoothed representations from 0-10 with whole numbers reflecting the assumed absolute copy number (ie. 0 represents homozygous deletions and 2 represents a normal copy number state)

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MMRC Reference Collection (35.1GB)

A comprehensive collection of expression, copy number, sequencing, and RNAi data. Multiple myeloma patient samples were collected by the Multiple Myeloma Research Consortium (MMRC), processed at the MMRC Tissue Bank at Mayo Clinic, Scottsdale, and analyzed at the Translational Genomics Research Institute, Phoenix (AZ) and the Broad Institute, Cambridge (MA).

MMRC gene expression profiles  (1.6GB) Gene expression  (In process) 

RNA from 304 patients with newly diagnosed and previously treated multiple myeloma was hybridized to Affymetrix U133 Plus 2.0 microarrays. The expression signals have been median centered and log2 normalized.

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MMRC copy number profiles  (6.5GB) Agilent aCGH  (In process) 

DNA from 254 patients with newly diagnosed and previously treated multiple myeloma was hybridized to Agilent 244K aCGH arrays. The data represent log2 ratios.

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TGen siRNA screen  (246.0KB) RNAi  (Published) 

KMS11 multiple myeloma cells were screened with multiple siRNAs targeting known and putative kinomes. A secondary screen was also performed.

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MMRC sequence data  (534.5KB) Resequencing  (Published) 

Tumor (CD138 selected) and normal (blood) DNA from 38 patients with multiple myeloma was subjected to whole exome (hybrid capture) or whole genome shotgun sequencing. One file contains all point mutations and indels affecting coding regions (estimated true positive rate of 95%) and another contains all structural re-arrangements supported by at least 3 good quality tumor reads (specificity to be determined, but likely in excess of 80%). The third is an Excel version of the file presented in the paper as Supplementary Table 3.

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MMRC sample annotation  (178.9KB) Sample annotation  (In process) 

Clinical information for patients who provided samples for gene expression or copy number profiling and/or sequencing.

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MMRC Sequence Data for mutation load  (177.0KB) Resequencing  (In process) 

slightly edited maf file for loading mutations into the DB

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MMRC sequence data 10/22/13  (4.0MB) Resequencing  (In process) 

Updated MMRC sequence data for 203 patients

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Methylation  (3.2MB) Undefined  (In process) 

Methylation data on 193 multiple myeloma MMGI samples using the GoldenGate Methylation Cancer Panel I (Illumina) for direct measurement of DNA methylation at 1,505 CpG sites selected from 807 genes

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Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy (53.6MB)

We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions.