DETAILED FISH PROFILING OF MULTIPLE MYELOMA PATIENTS IDENTIFIES A GROUP OF PATIENTS WITH ONLY SECONDARY CHROMOSOMAL ABERRATIONS
(Abstract release date: 05/19/16)
EHA Library. Pantic M. 06/09/16; 132804; E1255
Dr. Milena Pantic
Contributions
Contributions
Abstract
Abstract: E1255
Type: Eposter Presentation
Background
Using targeted fluorescence in situ hybridization (FISH) analyses of plasma cells, chromosomal aberrations are identified in more than 90% of patients (pts) with multiple myeloma (MM). It is postulated that early oncogenesis in MM is driven by two different (almost) exclusive genetic events: hyperdiploidy (HYP) and IGH translocations (IGH-R), and that clonal evolution occurs with acquisition of secondary aberrations (SA). Recent studies showed that some pts have both types of aberrations (IGH-R+HYP) and that myeloma relapses are sometimes related to clones quite different to those at diagnosis. However, the characteristics of MM pts with secondary aberrations only (SA) have not being extensively studied.
Aims
Our aim was to detect MM pts with SA and to analyze if these pts show different biological and clinical characteristics than MM pts with primary aberrations.
Methods
We performed FISH on CD138+ plasma cells of 163 MM pts consecutively diagnosed in our department since 2012. We used an extensive FISH panel to analyze five IGH-translocations, five different trisomies and five probes labeling recurrent secondary aberrations. Ten patients were analyzed by targeted next-generation sequencing (NGS) technology using the Agilent HaloPlex library preparation approach. Genes bearing hotspots for mutations in hematological malignancies were included in the sequencing panel.
Results
Chromosomal (chr) aberrations were detected in 98% (160/163) and hyperdiploidy was the most frequent primary aberration in 59% (94/160), IGH-R occurred in 29% (47/160) and SA in 12% (19/160) of MM pts. Overlapping IGH-R and HYP was found in three pts with HYP proceeding the developing of t(4;14), in line with recent publications (1,2). In comparison to all MM pts those with SA showed higher frequencies of IgA MM isotypes (6/19) and light chain-only MM (6/19). Moreover, they showed more aggressive MM with ISS3 in 74% (14/19) of pts at the time of analysis. 13q14 was the most frequent chromosomal locus involved in almost all pts (18/19) with equally distribution of deletion 13q14 (9/18) and monosomy 13 (9/18). Gain 1q21 was the second most frequent aberration present in even 68% (13/19) of SA pts. Deletion 1p32, cMYC and 14q32 (IGH)-abnormalities were discovered in 21% (4/19), 21% (4/19) and 26% (5/19), respectively. A total of 53 chr aberrations were detected in 19 MM pts with SA showing a high level of chr complexity compared to all MM pts. Interestingly, two of the analyzed pts, one with three SA and one with six, did not show additional mutations via NGS technology.
Conclusion
Our results reveal a progressive MM cell type with as yet unknown initiating oncogenetic events, but highly activated mechanisms of clonal proliferation. Moreover they raise two questions, 1. whether pts without detectable primary genetic events, but with occurrence of unfavorable and high-risk secondary cytogenetic lesions represent a distinct MM subgroup and 2. how these pts should be best assessed and treated. Using NGS technology in a large MM pt cohort should allow to gain more insight in the pathogenesis of this subgroup of MM pts.1. Pawlyn C. et al. Blood. 2015;125:831-402. Heuck C. et al Blood 2015;126(23)
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Plasma cells
Type: Eposter Presentation
Background
Using targeted fluorescence in situ hybridization (FISH) analyses of plasma cells, chromosomal aberrations are identified in more than 90% of patients (pts) with multiple myeloma (MM). It is postulated that early oncogenesis in MM is driven by two different (almost) exclusive genetic events: hyperdiploidy (HYP) and IGH translocations (IGH-R), and that clonal evolution occurs with acquisition of secondary aberrations (SA). Recent studies showed that some pts have both types of aberrations (IGH-R+HYP) and that myeloma relapses are sometimes related to clones quite different to those at diagnosis. However, the characteristics of MM pts with secondary aberrations only (SA) have not being extensively studied.
Aims
Our aim was to detect MM pts with SA and to analyze if these pts show different biological and clinical characteristics than MM pts with primary aberrations.
Methods
We performed FISH on CD138+ plasma cells of 163 MM pts consecutively diagnosed in our department since 2012. We used an extensive FISH panel to analyze five IGH-translocations, five different trisomies and five probes labeling recurrent secondary aberrations. Ten patients were analyzed by targeted next-generation sequencing (NGS) technology using the Agilent HaloPlex library preparation approach. Genes bearing hotspots for mutations in hematological malignancies were included in the sequencing panel.
Results
Chromosomal (chr) aberrations were detected in 98% (160/163) and hyperdiploidy was the most frequent primary aberration in 59% (94/160), IGH-R occurred in 29% (47/160) and SA in 12% (19/160) of MM pts. Overlapping IGH-R and HYP was found in three pts with HYP proceeding the developing of t(4;14), in line with recent publications (1,2). In comparison to all MM pts those with SA showed higher frequencies of IgA MM isotypes (6/19) and light chain-only MM (6/19). Moreover, they showed more aggressive MM with ISS3 in 74% (14/19) of pts at the time of analysis. 13q14 was the most frequent chromosomal locus involved in almost all pts (18/19) with equally distribution of deletion 13q14 (9/18) and monosomy 13 (9/18). Gain 1q21 was the second most frequent aberration present in even 68% (13/19) of SA pts. Deletion 1p32, cMYC and 14q32 (IGH)-abnormalities were discovered in 21% (4/19), 21% (4/19) and 26% (5/19), respectively. A total of 53 chr aberrations were detected in 19 MM pts with SA showing a high level of chr complexity compared to all MM pts. Interestingly, two of the analyzed pts, one with three SA and one with six, did not show additional mutations via NGS technology.
Conclusion
Our results reveal a progressive MM cell type with as yet unknown initiating oncogenetic events, but highly activated mechanisms of clonal proliferation. Moreover they raise two questions, 1. whether pts without detectable primary genetic events, but with occurrence of unfavorable and high-risk secondary cytogenetic lesions represent a distinct MM subgroup and 2. how these pts should be best assessed and treated. Using NGS technology in a large MM pt cohort should allow to gain more insight in the pathogenesis of this subgroup of MM pts.1. Pawlyn C. et al. Blood. 2015;125:831-402. Heuck C. et al Blood 2015;126(23)
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Plasma cells
Abstract: E1255
Type: Eposter Presentation
Background
Using targeted fluorescence in situ hybridization (FISH) analyses of plasma cells, chromosomal aberrations are identified in more than 90% of patients (pts) with multiple myeloma (MM). It is postulated that early oncogenesis in MM is driven by two different (almost) exclusive genetic events: hyperdiploidy (HYP) and IGH translocations (IGH-R), and that clonal evolution occurs with acquisition of secondary aberrations (SA). Recent studies showed that some pts have both types of aberrations (IGH-R+HYP) and that myeloma relapses are sometimes related to clones quite different to those at diagnosis. However, the characteristics of MM pts with secondary aberrations only (SA) have not being extensively studied.
Aims
Our aim was to detect MM pts with SA and to analyze if these pts show different biological and clinical characteristics than MM pts with primary aberrations.
Methods
We performed FISH on CD138+ plasma cells of 163 MM pts consecutively diagnosed in our department since 2012. We used an extensive FISH panel to analyze five IGH-translocations, five different trisomies and five probes labeling recurrent secondary aberrations. Ten patients were analyzed by targeted next-generation sequencing (NGS) technology using the Agilent HaloPlex library preparation approach. Genes bearing hotspots for mutations in hematological malignancies were included in the sequencing panel.
Results
Chromosomal (chr) aberrations were detected in 98% (160/163) and hyperdiploidy was the most frequent primary aberration in 59% (94/160), IGH-R occurred in 29% (47/160) and SA in 12% (19/160) of MM pts. Overlapping IGH-R and HYP was found in three pts with HYP proceeding the developing of t(4;14), in line with recent publications (1,2). In comparison to all MM pts those with SA showed higher frequencies of IgA MM isotypes (6/19) and light chain-only MM (6/19). Moreover, they showed more aggressive MM with ISS3 in 74% (14/19) of pts at the time of analysis. 13q14 was the most frequent chromosomal locus involved in almost all pts (18/19) with equally distribution of deletion 13q14 (9/18) and monosomy 13 (9/18). Gain 1q21 was the second most frequent aberration present in even 68% (13/19) of SA pts. Deletion 1p32, cMYC and 14q32 (IGH)-abnormalities were discovered in 21% (4/19), 21% (4/19) and 26% (5/19), respectively. A total of 53 chr aberrations were detected in 19 MM pts with SA showing a high level of chr complexity compared to all MM pts. Interestingly, two of the analyzed pts, one with three SA and one with six, did not show additional mutations via NGS technology.
Conclusion
Our results reveal a progressive MM cell type with as yet unknown initiating oncogenetic events, but highly activated mechanisms of clonal proliferation. Moreover they raise two questions, 1. whether pts without detectable primary genetic events, but with occurrence of unfavorable and high-risk secondary cytogenetic lesions represent a distinct MM subgroup and 2. how these pts should be best assessed and treated. Using NGS technology in a large MM pt cohort should allow to gain more insight in the pathogenesis of this subgroup of MM pts.1. Pawlyn C. et al. Blood. 2015;125:831-402. Heuck C. et al Blood 2015;126(23)
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Plasma cells
Type: Eposter Presentation
Background
Using targeted fluorescence in situ hybridization (FISH) analyses of plasma cells, chromosomal aberrations are identified in more than 90% of patients (pts) with multiple myeloma (MM). It is postulated that early oncogenesis in MM is driven by two different (almost) exclusive genetic events: hyperdiploidy (HYP) and IGH translocations (IGH-R), and that clonal evolution occurs with acquisition of secondary aberrations (SA). Recent studies showed that some pts have both types of aberrations (IGH-R+HYP) and that myeloma relapses are sometimes related to clones quite different to those at diagnosis. However, the characteristics of MM pts with secondary aberrations only (SA) have not being extensively studied.
Aims
Our aim was to detect MM pts with SA and to analyze if these pts show different biological and clinical characteristics than MM pts with primary aberrations.
Methods
We performed FISH on CD138+ plasma cells of 163 MM pts consecutively diagnosed in our department since 2012. We used an extensive FISH panel to analyze five IGH-translocations, five different trisomies and five probes labeling recurrent secondary aberrations. Ten patients were analyzed by targeted next-generation sequencing (NGS) technology using the Agilent HaloPlex library preparation approach. Genes bearing hotspots for mutations in hematological malignancies were included in the sequencing panel.
Results
Chromosomal (chr) aberrations were detected in 98% (160/163) and hyperdiploidy was the most frequent primary aberration in 59% (94/160), IGH-R occurred in 29% (47/160) and SA in 12% (19/160) of MM pts. Overlapping IGH-R and HYP was found in three pts with HYP proceeding the developing of t(4;14), in line with recent publications (1,2). In comparison to all MM pts those with SA showed higher frequencies of IgA MM isotypes (6/19) and light chain-only MM (6/19). Moreover, they showed more aggressive MM with ISS3 in 74% (14/19) of pts at the time of analysis. 13q14 was the most frequent chromosomal locus involved in almost all pts (18/19) with equally distribution of deletion 13q14 (9/18) and monosomy 13 (9/18). Gain 1q21 was the second most frequent aberration present in even 68% (13/19) of SA pts. Deletion 1p32, cMYC and 14q32 (IGH)-abnormalities were discovered in 21% (4/19), 21% (4/19) and 26% (5/19), respectively. A total of 53 chr aberrations were detected in 19 MM pts with SA showing a high level of chr complexity compared to all MM pts. Interestingly, two of the analyzed pts, one with three SA and one with six, did not show additional mutations via NGS technology.
Conclusion
Our results reveal a progressive MM cell type with as yet unknown initiating oncogenetic events, but highly activated mechanisms of clonal proliferation. Moreover they raise two questions, 1. whether pts without detectable primary genetic events, but with occurrence of unfavorable and high-risk secondary cytogenetic lesions represent a distinct MM subgroup and 2. how these pts should be best assessed and treated. Using NGS technology in a large MM pt cohort should allow to gain more insight in the pathogenesis of this subgroup of MM pts.1. Pawlyn C. et al. Blood. 2015;125:831-402. Heuck C. et al Blood 2015;126(23)
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Plasma cells
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