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| Status |
Public on Jul 22, 2016 |
| Title |
Phenotypic, transcriptomic and genomic characterization of clonal plasma cells in light chain amyloidosis [Copy number analysis] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Immunoglobulin light-chain amyloidosis (AL) is a rare clonal plasma cell (PC) disorder that remains largely incurable. AL and multiple myeloma (MM) share the same cellular origin, but while knowledge about MM PC biology has improved significantly, the same does not apply for AL. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 22 newly-diagnosed AL patients. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and MGUS or MM patients. However, in contrast to MM, highly-purified FACSs-sorted clonal PCs in AL (n=9/22) show virtually normal transcriptomes with only 68 deregulated genes as compared to normal PCs, including a few tumor suppressor (CDH1, RCAN) and pro-apoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11/22) were genomically unstable with a median of 9 copy-number-abnormities (CNAs) per case; many of which similar to those found in MM. Whole-exome sequencing (WES) was performed in three AL patients and revealed a median of 10 non-recurrent mutations per case. Altogether, we showed that although clonal PCs in AL display phenotypic and CNA profiles similar to MM, their transcriptome is remarkably similar to that of normal PCs. First-ever WES revealed the lack of a unifying mutation in AL
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| Overall design |
A total of 22 patients with confirmed diagnosis of AL based on the presence of amyloid-related systemic syndrome, positive amyloid tissue staining with Congo red, and evidence of PC clonality were studied. Samples were collected after informed consent was given, in accordance with local ethical committee guidelines and the Helsinki Declaration.
Genome-wide detection of CNAs and copy-number neutral loss-of-heterozygosity (LOH) were investigated using the Cytoscan 750K platform (Affymetrix) in 11/22 cases with adequate DNA extracted from FACS-sorted clonal PCs and paired T-lymphocytes. The AGCC and ChAS software programs (Affymetrix) were used for data analysis as described elsewhere. CNAs were reported when the three following criteria were met: ≥25 consecutive imbalanced markers per segment; ≥100Kb minimum genomic size and; <50% overlap with paired control DNA and/or genomic variants of Toronto DB (DGV). Only CNN-LOH larger that 5Mb, with ≥25 consecutive imbalanced markers per segment, and <50% overlap with patient-paired CNAs were considered.
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| Contributor(s) |
Paiva B, Martinez-Lopez J, Corchete LA, Puig N, Luz Sanchez M, Barcena P, Alignani D, Lasa M, García de Coca A, Pardal E, Escalante F, González-López TJ, Alonso J, Sierra M, Bárez A, Hernández J, Galende J, Prosper F, Orfao A, Vidriales M, Gutierrez NC, Mateos M, Lahuerta J, San Miguel JF |
| Citation(s) |
27069257 |
| Submission date |
Sep 15, 2015 |
| Last update date |
Jul 22, 2016 |
| Contact name |
Bruno Paiva |
| E-mail(s) |
bpaiva@unav.es
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| Organization name |
Clinica Universidad de Navarra
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| Street address |
Av. Pio XII, 55
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| City |
Pamplona |
| ZIP/Postal code |
31008 |
| Country |
Spain |
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| Platforms (1) |
| GPL18637 |
[CytoScan750K_Array] Affymetrix CytoScan 750K Array |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE73042 |
Phenotypic, transcriptomic and genomic characterization of clonal plasma cells in light chain amyloidosis |
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| Relations |
| BioProject |
PRJNA296101 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE73041_RAW.tar |
925.2 Mb |
(http)(custom) |
TAR (of CEL, CYCHP) |
| GSE73041_Weighted_Log2_Ratios_from_ChAS.txt.gz |
66.4 Mb |
(ftp)(http) |
TXT |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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