Transcriptomics

Dataset Information

1

Phenotypic, transcriptomic and genomic characterization of clonal plasma cells in light chain amyloidosis [Copy number analysis]


ABSTRACT: 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 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Felipe Prosper   Noemi Puig  Maria Luz Sanchez  Alfonso García de Coca  Abelardo Bárez  Alberto Orfao  Paloma Barcena  Maria-Belen Vidriales  Fernando Escalante  Norma C Gutierrez  Joaquin Martinez-Lopez  Diego Alignani  José Alonso  Josefina Galende  Marta Lasa  Emilia Pardal  Luis A Corchete  Jesús F San Miguel  Tomás J González-López  María-Victoria Mateos  Magdalena Sierra  José Hernández  Juan-Jose Lahuerta  Bruno Paiva 

PROVIDER: E-GEOD-73041 | ArrayExpress | 2016-07-22

SECONDARY ACCESSION(S): GSE73041PRJNA296101

REPOSITORIES: GEO, ArrayExpress

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Publications


Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated  ...[more]

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