ARRAY CGH ANALYSIS REVEALS DELETION OF CHROMOSOME 22Q11 IN CLL WITH NORMAL KARYOTYPE AND NO FISH ALTERATIONS.
(Abstract release date: 05/19/16)
EHA Library. Mestichelli F. 06/09/16; 132588; E1039
Dr. Francesca Mestichelli
Contributions
Contributions
Abstract
Abstract: E1039
Type: Eposter Presentation
Background
Genomic aberrations have increasingly gained importance as prognostic markers in B-cell chronic lymphocytic leukemia (CLL). Recently, a number of additional studies have been completed that clearly demonstrate the feasibility of using array comparative genomic Hybridization (a-CGH) as a clinical tool to identify genomic alterations of prognostic importance in CLL.
Aims
aCGH is able to identify a significant percentage of genomic abnormalities that escapes conventional cytogenetics and CLL FISH panel due to the limitations of these methods.
Methods
Using Oligonuckleotide-based array CGH (CytoChip 4x180K-Illumina) we detected copy number changes in the tumor genomes of 23 CLL cases at diagnosis, with normal karyotype e no FISH alterations. The cytogenetic study was performed on nuclei and metaphases after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin 2 (IL-2). In Chromosome Banding Analysis (CBA) we analyzed a minimum of 20 metaphases for each patient. Interphase FISH was performed using a comprehensive set of commercially available probes, as follows: P53 (TP53)Deletion (17p13), ATM Deletion (11q22), D13S25 Deletion (13q14.3), MYB Deletion (6q23)[Cytocell], CEP-12 (Chromosome 12) [Abbott], XL IGH plus Break Apart Probe [MetaSystems]. A minimum of 100–200 interphase nuclei were evaluated per probe for each patient.
Results
A total of 21 of the 23 (91%) cases were successfully analyzed by Oligonuckleotide-based array CGH. We observed a submicroscopic deletion of chromosome 22q11, as the sole anomaly in 4/21 cases (19%). Patients with loss 22q11 showed progression disease, and the median Time to Treatment (TT) was 64.2 months (range 24.6 - 83.1 months). Loss 22q11 ranged in size from 0.68Mb-0.28Mb. The minimally deleted region included the ZNF280A, ZNF280B, GGTLC2, and PRAME genes. Moreover this genomic change had not been detected by standard cytogenetic and/or FISH analyses. Gunn et al. suggest that the incidence of 22q11 deletions was second only to loss of the 13q14 region, found in approximately 50% of CLL cases; few and divergent data were reported in literature regarding prognostic impact of this genomic abnormality in CLL.
Conclusion
Our results showed that submicroscopic 22q11 deletion is potentially significant genomic aberration in CLL and this alteration is being missed by the current routine techniques. Moreover, increasing the number of cases to analyze we can confirm the data obtained and to correlate the alteration observed to the clinical course.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, Chronic lymphocytic leukemia
Type: Eposter Presentation
Background
Genomic aberrations have increasingly gained importance as prognostic markers in B-cell chronic lymphocytic leukemia (CLL). Recently, a number of additional studies have been completed that clearly demonstrate the feasibility of using array comparative genomic Hybridization (a-CGH) as a clinical tool to identify genomic alterations of prognostic importance in CLL.
Aims
aCGH is able to identify a significant percentage of genomic abnormalities that escapes conventional cytogenetics and CLL FISH panel due to the limitations of these methods.
Methods
Using Oligonuckleotide-based array CGH (CytoChip 4x180K-Illumina) we detected copy number changes in the tumor genomes of 23 CLL cases at diagnosis, with normal karyotype e no FISH alterations. The cytogenetic study was performed on nuclei and metaphases after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin 2 (IL-2). In Chromosome Banding Analysis (CBA) we analyzed a minimum of 20 metaphases for each patient. Interphase FISH was performed using a comprehensive set of commercially available probes, as follows: P53 (TP53)Deletion (17p13), ATM Deletion (11q22), D13S25 Deletion (13q14.3), MYB Deletion (6q23)[Cytocell], CEP-12 (Chromosome 12) [Abbott], XL IGH plus Break Apart Probe [MetaSystems]. A minimum of 100–200 interphase nuclei were evaluated per probe for each patient.
Results
A total of 21 of the 23 (91%) cases were successfully analyzed by Oligonuckleotide-based array CGH. We observed a submicroscopic deletion of chromosome 22q11, as the sole anomaly in 4/21 cases (19%). Patients with loss 22q11 showed progression disease, and the median Time to Treatment (TT) was 64.2 months (range 24.6 - 83.1 months). Loss 22q11 ranged in size from 0.68Mb-0.28Mb. The minimally deleted region included the ZNF280A, ZNF280B, GGTLC2, and PRAME genes. Moreover this genomic change had not been detected by standard cytogenetic and/or FISH analyses. Gunn et al. suggest that the incidence of 22q11 deletions was second only to loss of the 13q14 region, found in approximately 50% of CLL cases; few and divergent data were reported in literature regarding prognostic impact of this genomic abnormality in CLL.
Conclusion
Our results showed that submicroscopic 22q11 deletion is potentially significant genomic aberration in CLL and this alteration is being missed by the current routine techniques. Moreover, increasing the number of cases to analyze we can confirm the data obtained and to correlate the alteration observed to the clinical course.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, Chronic lymphocytic leukemia
Abstract: E1039
Type: Eposter Presentation
Background
Genomic aberrations have increasingly gained importance as prognostic markers in B-cell chronic lymphocytic leukemia (CLL). Recently, a number of additional studies have been completed that clearly demonstrate the feasibility of using array comparative genomic Hybridization (a-CGH) as a clinical tool to identify genomic alterations of prognostic importance in CLL.
Aims
aCGH is able to identify a significant percentage of genomic abnormalities that escapes conventional cytogenetics and CLL FISH panel due to the limitations of these methods.
Methods
Using Oligonuckleotide-based array CGH (CytoChip 4x180K-Illumina) we detected copy number changes in the tumor genomes of 23 CLL cases at diagnosis, with normal karyotype e no FISH alterations. The cytogenetic study was performed on nuclei and metaphases after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin 2 (IL-2). In Chromosome Banding Analysis (CBA) we analyzed a minimum of 20 metaphases for each patient. Interphase FISH was performed using a comprehensive set of commercially available probes, as follows: P53 (TP53)Deletion (17p13), ATM Deletion (11q22), D13S25 Deletion (13q14.3), MYB Deletion (6q23)[Cytocell], CEP-12 (Chromosome 12) [Abbott], XL IGH plus Break Apart Probe [MetaSystems]. A minimum of 100–200 interphase nuclei were evaluated per probe for each patient.
Results
A total of 21 of the 23 (91%) cases were successfully analyzed by Oligonuckleotide-based array CGH. We observed a submicroscopic deletion of chromosome 22q11, as the sole anomaly in 4/21 cases (19%). Patients with loss 22q11 showed progression disease, and the median Time to Treatment (TT) was 64.2 months (range 24.6 - 83.1 months). Loss 22q11 ranged in size from 0.68Mb-0.28Mb. The minimally deleted region included the ZNF280A, ZNF280B, GGTLC2, and PRAME genes. Moreover this genomic change had not been detected by standard cytogenetic and/or FISH analyses. Gunn et al. suggest that the incidence of 22q11 deletions was second only to loss of the 13q14 region, found in approximately 50% of CLL cases; few and divergent data were reported in literature regarding prognostic impact of this genomic abnormality in CLL.
Conclusion
Our results showed that submicroscopic 22q11 deletion is potentially significant genomic aberration in CLL and this alteration is being missed by the current routine techniques. Moreover, increasing the number of cases to analyze we can confirm the data obtained and to correlate the alteration observed to the clinical course.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, Chronic lymphocytic leukemia
Type: Eposter Presentation
Background
Genomic aberrations have increasingly gained importance as prognostic markers in B-cell chronic lymphocytic leukemia (CLL). Recently, a number of additional studies have been completed that clearly demonstrate the feasibility of using array comparative genomic Hybridization (a-CGH) as a clinical tool to identify genomic alterations of prognostic importance in CLL.
Aims
aCGH is able to identify a significant percentage of genomic abnormalities that escapes conventional cytogenetics and CLL FISH panel due to the limitations of these methods.
Methods
Using Oligonuckleotide-based array CGH (CytoChip 4x180K-Illumina) we detected copy number changes in the tumor genomes of 23 CLL cases at diagnosis, with normal karyotype e no FISH alterations. The cytogenetic study was performed on nuclei and metaphases after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin 2 (IL-2). In Chromosome Banding Analysis (CBA) we analyzed a minimum of 20 metaphases for each patient. Interphase FISH was performed using a comprehensive set of commercially available probes, as follows: P53 (TP53)Deletion (17p13), ATM Deletion (11q22), D13S25 Deletion (13q14.3), MYB Deletion (6q23)[Cytocell], CEP-12 (Chromosome 12) [Abbott], XL IGH plus Break Apart Probe [MetaSystems]. A minimum of 100–200 interphase nuclei were evaluated per probe for each patient.
Results
A total of 21 of the 23 (91%) cases were successfully analyzed by Oligonuckleotide-based array CGH. We observed a submicroscopic deletion of chromosome 22q11, as the sole anomaly in 4/21 cases (19%). Patients with loss 22q11 showed progression disease, and the median Time to Treatment (TT) was 64.2 months (range 24.6 - 83.1 months). Loss 22q11 ranged in size from 0.68Mb-0.28Mb. The minimally deleted region included the ZNF280A, ZNF280B, GGTLC2, and PRAME genes. Moreover this genomic change had not been detected by standard cytogenetic and/or FISH analyses. Gunn et al. suggest that the incidence of 22q11 deletions was second only to loss of the 13q14 region, found in approximately 50% of CLL cases; few and divergent data were reported in literature regarding prognostic impact of this genomic abnormality in CLL.
Conclusion
Our results showed that submicroscopic 22q11 deletion is potentially significant genomic aberration in CLL and this alteration is being missed by the current routine techniques. Moreover, increasing the number of cases to analyze we can confirm the data obtained and to correlate the alteration observed to the clinical course.
Session topic: E-poster
Keyword(s): Array based comparative genomic hybridization, Chronic lymphocytic leukemia
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