title: Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization are complementary techniques to detect cytogenetic abnormalities in multiple myeloma.
abstract: Multiple myeloma (MM) is a genetically heterogeneous disease with diverse clinical outcomes. Interphase fluorescence in situ hybridization (i-FISH) is the most commonly used approach to detect recurrent cytogenetic abnormalities in this malignancy. We aimed to assess the performance of multiplex ligation-dependent probe amplification (MLPA) to reveal copy number abnormalities (CNAs) in MM. Diagnostic bone marrow samples from 81 patients were analyzed using 42 MLPA probes for the following regions: 1p32-31, 1p21, 1q21.3, 1q23.3, 5q31.3, 12p13.31, 13q14, 16q12, 16q23, and 17p13. All samples were also screened by i-FISH for the presence of hyperdiploidy, deletion/monosomy of chromosome 13, deletion of TP53, disruption of the immunoglobulin heavy-chain gene, t(4;14), t(11;14), t(14;16), t(8;14), gain of 5q and abnormalities of chromosome 1. A total of 245 alterations were detected in 79 cases (98%). Investigating the same aberrations, the two methods showed a congruency of higher than 90%. A low proportion of cells with the relevant abnormality, focal CNAs and unmatched probes were responsible for the discrepancies. MLPA revealed 95 CNAs not detected by i-FISH providing additional information in 53 cases (65%). Scrutiny of CNAs on chromosome 1, using more than 20 probes, revealed significant heterogeneity in size and location, and variable intra-chromosomal and intra-clonal rates of loss or gain. Our results suggest that MLPA is a reliable high-throughput technique to detect CNAs in MM. Since balanced aberrations are key to prognostic classification of this disease, MLPA and i-FISH should be applied as complementary techniques in diagnostic pathology.
authors.affiliation: Department of Pathology, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Donat
authors.initials: D
authors.lastname: Alpar
authors.forename: Danielle
authors.initials: D
authors.lastname: de Jong
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Holczer-Nagy
authors.forename: Bela
authors.initials: B
authors.lastname: Kajtar
authors.forename: Suvi
authors.initials: S
authors.lastname: Savola
authors.forename: Pal
authors.initials: P
authors.lastname: Jakso
authors.forename: Marianna
authors.initials: M
authors.lastname: David
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Kosztolanyi
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kereskai
authors.forename: Laszlo
authors.initials: L
authors.lastname: Pajor
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
mesh_terms: D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D020732:Cytogenetic Analysis / Q000379:methods*; D056915:DNA Copy Number Variations; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D060885:Multiplex Polymerase Chain Reaction