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Cancer Genet. 2020 Jan 11. pii: S2210-7762(19)30521-6. doi: 10.1016/j.cancergen.2020.01.001. [Epub ahead of print]

The combination of WGS and RNA-Seq is superior to conventional diagnostic tests in multiple myeloma: Ready for prime time?

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MLL Munich Leukemia Laboratory, Munich, Germany.
MLL Munich Leukemia Laboratory, Munich, Germany; Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC) Campus Universitario Miguel de Unamuno, Salamanca, Spain.
MLL Munich Leukemia Laboratory, Munich, Germany. Electronic address:


The diagnosis and risk stratification of multiple myeloma (MM) is based on clinical and cytogenetic tests. Magnetic CD138 enrichment followed by interphase FISH (fluorescence in situ hybridisation) is the gold standard to identify prognostic translocations and copy number alterations (CNA). Although clinical implications of gene expression profiling (GEP) or panel based sequencing results are evident, those tests have not yet reached routine clinical application. We set up a single workflow to analyse MM of 211 patients at first diagnosis by whole genome sequencing (WGS) and RNA-Seq and validate the results by FISH analysis. We observed a 96% concordance of FISH and WGS results when assessing translocations involving the IGH locus and an overall concordance of FISH and WGS of 92% when assessing CNA. WGS analysis resulted in the identification of 17 additional MYC-translocations that were missed by FISH analysis. RNA-Seq followed by supervised clustering grouped patients in their expected genetically defined subgroup and prompted the assessment of WGS data in cases that were not congruent with FISH. This allowed the identification of additional IGH-translocations and hyperdiploid cases. We show the reliability of WGS an RNA-Seq in a clinical setting, which is a prerequisite for a novel routine diagnostic test.


FISH; Multiple myeloma; RNA-Seq; Risk stratification; Whole genome sequencing

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Conflict of interest statement

Declaration of Competing Interest The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript

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