High-Throughput Copy Number Profiling by Digital Multiplex Ligation-Dependent Probe Amplification in Multiple Myeloma

Publication date: Available online 8 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Szabolcs Kosztolanyi, Richard Kiss, Lilit Atanesyan, Ambrus Gango, Karel de Groot, Maryvonne Steenkamer, Pal Jakso, Andras Matolcsy, Bela Kajtar, Laszlo Pajor, Karoly Szuhai, Suvi Savola, Csaba Bodor, Donat AlparAbstractMultiple myeloma (MM) is a genetically heterogeneous disease with diverse clinical outcome. Copy number alterations (CNAs) including whole chromosome and subchromosomal gains and losses are common contributors of the pathogenesis and have demonstrated prognostic impact in MM. We tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA), a novel technique combining MLPA and next-generation sequencing, to detect disease-related CNAs. Copy number status at 371 genomic loci were simultaneously analyzed in 56 diagnostic bone marrow samples which were also examined by conventional MLPA and interphase fluorescence in situ hybridization (iFISH). On average, digitalMLPA identified 4.4 subchromosomal CNAs per patient. The increased number of probes as compared to conventional MLPA allowed a detailed mapping of CNAs, especially on chromosome 1 where 24 different patterns were observed in 38 patients harboring loss(1p) and/or gain(1q). IFISH, MLPA, and digitalMLPA results at loci investigated by multiple methods showed a congruency of 95%. Besides precise characterization of hyperdiploid karyotypes not efficiently achievable by iFIS...

Source: The Journal of Molecular Diagnostics - August 8, 2018 Category: Pathology Source Type: research