Ultra-low depth sequencing of plasma cell DNA for the detection of copy number aberrations in multiple myeloma.


Journal

Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329

Informations de publication

Date de publication:
08 2020
Historique:
received: 28 12 2019
revised: 22 03 2020
accepted: 01 04 2020
pubmed: 8 4 2020
medline: 7 7 2021
entrez: 8 4 2020
Statut: ppublish

Résumé

Cytogenetic abnormalities are powerful prognostic factors in multiple myeloma (MM) and are routinely analyzed by FISH on bone marrow (BM) plasma cells (PC). Although considered the gold standard, FISH experiments can be laborious and expensive. Therefore, array-CGH (aCGH) has been introduced as an alternative approach for detecting copy number aberrations (CNA), reducing the number of FISH experiments per case and yielding genome-wide information. Currently, next generation sequencing (NGS) technologies offer new perspectives for the diagnostic workup of malignant disorders. In this study, we examined ultra-low depth whole genome sequencing (LDS) as a valid alternative for aCGH for the detection of CNA in BM PC in MM. To this end, BM aspirates obtained in a diagnostic setting from 20 MM cases were analyzed. CD138+ cell-sorted samples were subjected to FISH analysis. DNA was extracted for subsequent aCGH and LDS analysis. CNA were detected by aCGH and LDS in all but one case. Importantly, all CNA identified by parallel first generation aCGH analysis were also detected by LDS, along with six additional CNA in five cases. One of these additional aberrations was in a region of prognostic importance in MM and was confirmed using FISH. However, risk stratification in these particular cases was unaffected. Thus, a perfectly concordant prognostication between array-CGH and LDS was observed. This validates LDS as a novel and cost-efficient tool for the detection of CNA in MM.

Identifiants

pubmed: 32259320
doi: 10.1002/gcc.22848
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

465-471

Informations de copyright

© 2020 Wiley Periodicals, Inc.

Références

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Auteurs

Lieselot Buedts (L)

Center for Human Genetics, KU Leuven, Leuven, Belgium.

Sanne Smits (S)

Center for Human Genetics, KU Leuven, Leuven, Belgium.

Geneviève Ameye (G)

Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.

Stefan Lehnert (S)

Genomics Core, KU Leuven, Leuven, Belgium.

Jia Ding (J)

Genomics Core, KU Leuven, Leuven, Belgium.

Michel Delforge (M)

Department of Hematology, University Hospitals Leuven, Leuven, Belgium.

Joris Vermeesch (J)

Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
Genomics Core, KU Leuven, Leuven, Belgium.

Nancy Boeckx (N)

Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
Department of Oncology, KU Leuven, Leuven, Belgium.

Thomas Tousseyn (T)

Department of Pathology, University Hospitals Leuven, Leuven, Belgium.

Lucienne Michaux (L)

Center for Human Genetics, KU Leuven, Leuven, Belgium.
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.

Peter Vandenberghe (P)

Center for Human Genetics, KU Leuven, Leuven, Belgium.
Department of Hematology, University Hospitals Leuven, Leuven, Belgium.

Barbara Dewaele (B)

Center for Human Genetics, KU Leuven, Leuven, Belgium.
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.

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