IDENTIFICATION OF PROGNOSTIC RELEVANT GENETIC ABNORMALITIES IN MULTIPLE MYELOMA USING MICROARRAY-BASED GENOMIC PROFILING IN ROUTINE DIAGNOSTICS
(Abstract release date: 05/19/16)
EHA Library. Poddighe P. 06/09/16; 134835; PB1935
Dr. Pino Poddighe
Contributions
Contributions
Abstract
Abstract: PB1935
Type: Publication Only
Background
Multiple myeloma (MM) is a neoplasm that exhibits a broad heterogeneity in both biological behavior and clinical presentation. Specific copy number abnormalities (CNAs) such as hyperdiploidy, 1p loss, 1q gain, 13q loss and 17p (TP53) loss, and IGH translocations, such as t(4;14)(p16;q32) and t(14;16)(q32;q23), play key roles in the pathogenesis of MM and, in addition, provide important information on its prognosis and treatment response. In routine diagnostics such prognostic relevant chromosomal abnormalities are detected by interphase fluorescence in situ hybridization (iFISH) on enriched plasma cells. However, iFISH analysis of multiple loci is laborious and provides only genetic information of the probe targets. Microarray-based whole genome profiling, on the other hand, will provide genome-wide genetic information, allowing the detection of small (cryptic) copy number alterations (CNAs) and copy neutral loss of heterozygosity (CNLOH), that are nor identified by targeted iFISH.
Aims
In this study we wanted to validate the detection of prognostic relevant copy number aberrations in MM by micro-array based genomic profiling.
Methods
We subjected 37 MM samples to iFISH with the diagnostic probe for the detection of prognostic relevant CNA, i.e. D5S23/D5S721/CEP9/CEP15 for ploidy assessment, LSI 13 (13q14) for the identification of loss of 13q, LSI TP53 (17p13.1) for the identification of loss of 17p, and CDKN2C/CKS1B for the identification of loss of 1p32 and gain of 1q21. Next, we performed microarray-based genomic profiling using the high density SNP-based CytoScan HD array platform.
Results
All prognostic relevant CNAs as detected by iFISH were also observed by microarray-based whole genome profiling. Micro-array was able to detect small clones with CNA, present in only 15% of the cells, which was lower than the EMN-proposed detection limit of 20% for CNA. In addition, in four cases micro-array revealed a copy neutral loss of heterozygosity (CNLOH), and in four other cases a 1p21 or 1p16 loss, which was outside the 1p32 iFISH target region.
Conclusion
In routine diagnostics the micro-array approach is a good and fast alternative for iFISH for the detection of prognostic relevant CNAs in multiple myeloma.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, FISH, Multiple myeloma
Type: Publication Only
Background
Multiple myeloma (MM) is a neoplasm that exhibits a broad heterogeneity in both biological behavior and clinical presentation. Specific copy number abnormalities (CNAs) such as hyperdiploidy, 1p loss, 1q gain, 13q loss and 17p (TP53) loss, and IGH translocations, such as t(4;14)(p16;q32) and t(14;16)(q32;q23), play key roles in the pathogenesis of MM and, in addition, provide important information on its prognosis and treatment response. In routine diagnostics such prognostic relevant chromosomal abnormalities are detected by interphase fluorescence in situ hybridization (iFISH) on enriched plasma cells. However, iFISH analysis of multiple loci is laborious and provides only genetic information of the probe targets. Microarray-based whole genome profiling, on the other hand, will provide genome-wide genetic information, allowing the detection of small (cryptic) copy number alterations (CNAs) and copy neutral loss of heterozygosity (CNLOH), that are nor identified by targeted iFISH.
Aims
In this study we wanted to validate the detection of prognostic relevant copy number aberrations in MM by micro-array based genomic profiling.
Methods
We subjected 37 MM samples to iFISH with the diagnostic probe for the detection of prognostic relevant CNA, i.e. D5S23/D5S721/CEP9/CEP15 for ploidy assessment, LSI 13 (13q14) for the identification of loss of 13q, LSI TP53 (17p13.1) for the identification of loss of 17p, and CDKN2C/CKS1B for the identification of loss of 1p32 and gain of 1q21. Next, we performed microarray-based genomic profiling using the high density SNP-based CytoScan HD array platform.
Results
All prognostic relevant CNAs as detected by iFISH were also observed by microarray-based whole genome profiling. Micro-array was able to detect small clones with CNA, present in only 15% of the cells, which was lower than the EMN-proposed detection limit of 20% for CNA. In addition, in four cases micro-array revealed a copy neutral loss of heterozygosity (CNLOH), and in four other cases a 1p21 or 1p16 loss, which was outside the 1p32 iFISH target region.
Conclusion
In routine diagnostics the micro-array approach is a good and fast alternative for iFISH for the detection of prognostic relevant CNAs in multiple myeloma.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, FISH, Multiple myeloma
Abstract: PB1935
Type: Publication Only
Background
Multiple myeloma (MM) is a neoplasm that exhibits a broad heterogeneity in both biological behavior and clinical presentation. Specific copy number abnormalities (CNAs) such as hyperdiploidy, 1p loss, 1q gain, 13q loss and 17p (TP53) loss, and IGH translocations, such as t(4;14)(p16;q32) and t(14;16)(q32;q23), play key roles in the pathogenesis of MM and, in addition, provide important information on its prognosis and treatment response. In routine diagnostics such prognostic relevant chromosomal abnormalities are detected by interphase fluorescence in situ hybridization (iFISH) on enriched plasma cells. However, iFISH analysis of multiple loci is laborious and provides only genetic information of the probe targets. Microarray-based whole genome profiling, on the other hand, will provide genome-wide genetic information, allowing the detection of small (cryptic) copy number alterations (CNAs) and copy neutral loss of heterozygosity (CNLOH), that are nor identified by targeted iFISH.
Aims
In this study we wanted to validate the detection of prognostic relevant copy number aberrations in MM by micro-array based genomic profiling.
Methods
We subjected 37 MM samples to iFISH with the diagnostic probe for the detection of prognostic relevant CNA, i.e. D5S23/D5S721/CEP9/CEP15 for ploidy assessment, LSI 13 (13q14) for the identification of loss of 13q, LSI TP53 (17p13.1) for the identification of loss of 17p, and CDKN2C/CKS1B for the identification of loss of 1p32 and gain of 1q21. Next, we performed microarray-based genomic profiling using the high density SNP-based CytoScan HD array platform.
Results
All prognostic relevant CNAs as detected by iFISH were also observed by microarray-based whole genome profiling. Micro-array was able to detect small clones with CNA, present in only 15% of the cells, which was lower than the EMN-proposed detection limit of 20% for CNA. In addition, in four cases micro-array revealed a copy neutral loss of heterozygosity (CNLOH), and in four other cases a 1p21 or 1p16 loss, which was outside the 1p32 iFISH target region.
Conclusion
In routine diagnostics the micro-array approach is a good and fast alternative for iFISH for the detection of prognostic relevant CNAs in multiple myeloma.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, FISH, Multiple myeloma
Type: Publication Only
Background
Multiple myeloma (MM) is a neoplasm that exhibits a broad heterogeneity in both biological behavior and clinical presentation. Specific copy number abnormalities (CNAs) such as hyperdiploidy, 1p loss, 1q gain, 13q loss and 17p (TP53) loss, and IGH translocations, such as t(4;14)(p16;q32) and t(14;16)(q32;q23), play key roles in the pathogenesis of MM and, in addition, provide important information on its prognosis and treatment response. In routine diagnostics such prognostic relevant chromosomal abnormalities are detected by interphase fluorescence in situ hybridization (iFISH) on enriched plasma cells. However, iFISH analysis of multiple loci is laborious and provides only genetic information of the probe targets. Microarray-based whole genome profiling, on the other hand, will provide genome-wide genetic information, allowing the detection of small (cryptic) copy number alterations (CNAs) and copy neutral loss of heterozygosity (CNLOH), that are nor identified by targeted iFISH.
Aims
In this study we wanted to validate the detection of prognostic relevant copy number aberrations in MM by micro-array based genomic profiling.
Methods
We subjected 37 MM samples to iFISH with the diagnostic probe for the detection of prognostic relevant CNA, i.e. D5S23/D5S721/CEP9/CEP15 for ploidy assessment, LSI 13 (13q14) for the identification of loss of 13q, LSI TP53 (17p13.1) for the identification of loss of 17p, and CDKN2C/CKS1B for the identification of loss of 1p32 and gain of 1q21. Next, we performed microarray-based genomic profiling using the high density SNP-based CytoScan HD array platform.
Results
All prognostic relevant CNAs as detected by iFISH were also observed by microarray-based whole genome profiling. Micro-array was able to detect small clones with CNA, present in only 15% of the cells, which was lower than the EMN-proposed detection limit of 20% for CNA. In addition, in four cases micro-array revealed a copy neutral loss of heterozygosity (CNLOH), and in four other cases a 1p21 or 1p16 loss, which was outside the 1p32 iFISH target region.
Conclusion
In routine diagnostics the micro-array approach is a good and fast alternative for iFISH for the detection of prognostic relevant CNAs in multiple myeloma.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, FISH, Multiple myeloma
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