The Combination of WGS and RNA-Seq is Superior to Conventional Diagnostic Tests in Multiple Myeloma: Ready for Prime Time?

Publication date: Available online 11 January 2020Source: Cancer GeneticsAuthor(s): Alexander Höllein, Sven O. Twardziok, Wencke Walter, Stephan Hutter, Constance Baer, Jesus Maria Hernandez-Sanchez, Manja Meggendorfer, Torsten Haferlach, Wolfgang Kern, Claudia HaferlachAbstractThe 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 rel...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research