Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization are complementary techniques to detect cytogenetic abnormalities in multiple myeloma

Donat Alpar, Danielle de Jong, Zsofia Holczer-Nagy, Bela Kajtar, Suvi Savola, Pal Jakso, Marianna David, Szabolcs Kosztolanyi, L. Kereskai, Laszlo Pajor, Karoly Szuhai

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)785-793
Number of pages9
JournalGenes Chromosomes and Cancer
Volume52
Issue number9
DOIs
Publication statusPublished - Sep 2013

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Multiplex Polymerase Chain Reaction
Multiple Myeloma
Fluorescence In Situ Hybridization
Chromosome Aberrations
Interphase
Chromosomes, Human, Pair 1
Immunoglobulin Heavy Chain Genes
Monosomy
Chromosomes, Human, Pair 13
Chromosome Deletion
Polyploidy
Bone Marrow
Pathology
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization are complementary techniques to detect cytogenetic abnormalities in multiple myeloma. / Alpar, Donat; de Jong, Danielle; Holczer-Nagy, Zsofia; Kajtar, Bela; Savola, Suvi; Jakso, Pal; David, Marianna; Kosztolanyi, Szabolcs; Kereskai, L.; Pajor, Laszlo; Szuhai, Karoly.

In: Genes Chromosomes and Cancer, Vol. 52, No. 9, 09.2013, p. 785-793.

Research output: Contribution to journalArticle

Alpar, Donat ; de Jong, Danielle ; Holczer-Nagy, Zsofia ; Kajtar, Bela ; Savola, Suvi ; Jakso, Pal ; David, Marianna ; Kosztolanyi, Szabolcs ; Kereskai, L. ; Pajor, Laszlo ; Szuhai, Karoly. / Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization are complementary techniques to detect cytogenetic abnormalities in multiple myeloma. In: Genes Chromosomes and Cancer. 2013 ; Vol. 52, No. 9. pp. 785-793.
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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.",
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AU - Kajtar, Bela

AU - Savola, Suvi

AU - Jakso, Pal

AU - David, Marianna

AU - Kosztolanyi, Szabolcs

AU - Kereskai, L.

AU - Pajor, Laszlo

AU - Szuhai, Karoly

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AB - 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.

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