GENOME-WIDE ANALYSIS OF SINGLE NUCLEOTIDE POLYMORPHISM (SNPS) IN PATIENTS WITH DE NOVO ACUTE MYELOID LEUKEMIA WITH NORMAL KARYOTYPE
(Abstract release date: 05/19/16)
EHA Library. Ibañez M. 06/09/16; 132449; E900
Dr. Mariam Ibañez
Contributions
Contributions
Abstract
Abstract: E900
Type: Eposter Presentation
Background
Although recurrent chromosomal alterations are the main diagnostic and prognostic markers in acute myeloid leukemia (AML) at the time of diagnosis, nearly 50% of patients have an apparently normal karyotype (NKAML), displaying an intermediate risk for survival and relapse. SNP array (SNP-A) allow us to study variations in the number of copies (CNV) and regions of loss of heterozygozity (LOH) in myeloid neoplasms. Using systematically matched germline samples might ascertain the somatic nature of each lesion.
Aims
To establish the role that may play some cryptic abnormalities present in NKAML patients through the frequency, recurrence and any possible clinical association of CNVs and LOHs.
Methods
A total of 218 de novo NKAML patients were analyzed. Among them, 25 patients were enrolled in the consecutive multicenter PETHEMA trials at the Hospital Universitari i Politècnic La Fe and Hospital 12 de Octubre, with available DNA sample at diagnosis and at complete molecular remission were selected for this study. DNA from Hospital Universitari i Politècnic La Fe were provided by Biobank La Fe. We expanded the cohort with other AML series with publicly available SNP-A data to a total of 181 cases (n=49 del TCGA,a n=53 de Kronke J, et al.,b n=30 de Tadayuki A, et al.c y n=49 Koren-Michowitz M, et al.d). Samples were genotyped using Human CytoScan HD (n=37) and Genome-Wide Human SNP 6.0 (n=181) according to manufacturer’s protocol (Affymetrix Santa Clara, C.A., U.S.A.). DNA copy number and paired LOH analyses were performed using the Genotyping Console and the Chromosome Analyses Suite (ChAS) software (Affymetrix). Filters applied for segment Copy Number Abnormalities (CNA) detection were ≥20 consecutive markers in a region of at least 100Kb, and for regions of Copy Neutral Loss of Heterozygocity (CN-LOH), ≥100 markers in at least 500Kb. All abnormalities found in the remission sample were ruled out and assume as non-somatic. Besides, every potential abnormality was checked in the Database of Genomic Variants (http://projects.tcag.ca/variation). Size, position, and location of genes were identified with UCSC Genome Browser (http://genome.ucsc.edu/). The human reference sequence used for alignment was the GRCh37/hg19assembly
Results
A total of 304 abnormalities were found as an acquired event in 143 NKAML patients (66%), resulting in 2.1 abnormalities/case. These consisted of 151 heterozygous deletions, 99duplications and 54 CN-LOH. Cryptic chromosomal aberrations were more frequents in chr 1, 2, 5, 6, 7, 11, 13, 16 and 19. The most common CN-LOH was in 13q (being FLT3 involved in all them), 1p y 7p. In 19p (chr19:1-16300000) we detected more deletions, while in chr 1, 4, 5 and 20 more insertions. Likewise, patients harbored cryptic aberrations (mainly deletions or CN-LOH) involving KMT2A,(n=5), RAD21 (n=4), RUNX1 (n=4), ETV6 (n=3), EZH2 (n=3), WT1 (n=3), PTPN11 (n=2), TET2 (n=2), U2AF1 (n=2), IDH1 (n=1) and NPM1 (n=1). Further results will be presented.
Conclusion
This study has delineated recurrent abnormalities that may act as driver event and could explain leukemogenesis in up to 66% of NKAML cases. This work was supported by the following grants: Fundación Española de Hematología (FEHH), PI12/01047, RD12/0036/0014, PIE13/00046, PI13/01640, PI13/02837, PT13/0010/0026, PI14//01649 and PROMETEOII/2014/025a. N Engl J Med 2013; 368:2059–2074.b. Blood. 2013, 122 (1): 100-8.c. Haematologica. 2009, 94(2): 213-23.d. Leuk Res. 2012, 36(4): 467-73.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
Type: Eposter Presentation
Background
Although recurrent chromosomal alterations are the main diagnostic and prognostic markers in acute myeloid leukemia (AML) at the time of diagnosis, nearly 50% of patients have an apparently normal karyotype (NKAML), displaying an intermediate risk for survival and relapse. SNP array (SNP-A) allow us to study variations in the number of copies (CNV) and regions of loss of heterozygozity (LOH) in myeloid neoplasms. Using systematically matched germline samples might ascertain the somatic nature of each lesion.
Aims
To establish the role that may play some cryptic abnormalities present in NKAML patients through the frequency, recurrence and any possible clinical association of CNVs and LOHs.
Methods
A total of 218 de novo NKAML patients were analyzed. Among them, 25 patients were enrolled in the consecutive multicenter PETHEMA trials at the Hospital Universitari i Politècnic La Fe and Hospital 12 de Octubre, with available DNA sample at diagnosis and at complete molecular remission were selected for this study. DNA from Hospital Universitari i Politècnic La Fe were provided by Biobank La Fe. We expanded the cohort with other AML series with publicly available SNP-A data to a total of 181 cases (n=49 del TCGA,a n=53 de Kronke J, et al.,b n=30 de Tadayuki A, et al.c y n=49 Koren-Michowitz M, et al.d). Samples were genotyped using Human CytoScan HD (n=37) and Genome-Wide Human SNP 6.0 (n=181) according to manufacturer’s protocol (Affymetrix Santa Clara, C.A., U.S.A.). DNA copy number and paired LOH analyses were performed using the Genotyping Console and the Chromosome Analyses Suite (ChAS) software (Affymetrix). Filters applied for segment Copy Number Abnormalities (CNA) detection were ≥20 consecutive markers in a region of at least 100Kb, and for regions of Copy Neutral Loss of Heterozygocity (CN-LOH), ≥100 markers in at least 500Kb. All abnormalities found in the remission sample were ruled out and assume as non-somatic. Besides, every potential abnormality was checked in the Database of Genomic Variants (http://projects.tcag.ca/variation). Size, position, and location of genes were identified with UCSC Genome Browser (http://genome.ucsc.edu/). The human reference sequence used for alignment was the GRCh37/hg19assembly
Results
A total of 304 abnormalities were found as an acquired event in 143 NKAML patients (66%), resulting in 2.1 abnormalities/case. These consisted of 151 heterozygous deletions, 99duplications and 54 CN-LOH. Cryptic chromosomal aberrations were more frequents in chr 1, 2, 5, 6, 7, 11, 13, 16 and 19. The most common CN-LOH was in 13q (being FLT3 involved in all them), 1p y 7p. In 19p (chr19:1-16300000) we detected more deletions, while in chr 1, 4, 5 and 20 more insertions. Likewise, patients harbored cryptic aberrations (mainly deletions or CN-LOH) involving KMT2A,(n=5), RAD21 (n=4), RUNX1 (n=4), ETV6 (n=3), EZH2 (n=3), WT1 (n=3), PTPN11 (n=2), TET2 (n=2), U2AF1 (n=2), IDH1 (n=1) and NPM1 (n=1). Further results will be presented.
Conclusion
This study has delineated recurrent abnormalities that may act as driver event and could explain leukemogenesis in up to 66% of NKAML cases. This work was supported by the following grants: Fundación Española de Hematología (FEHH), PI12/01047, RD12/0036/0014, PIE13/00046, PI13/01640, PI13/02837, PT13/0010/0026, PI14//01649 and PROMETEOII/2014/025a. N Engl J Med 2013; 368:2059–2074.b. Blood. 2013, 122 (1): 100-8.c. Haematologica. 2009, 94(2): 213-23.d. Leuk Res. 2012, 36(4): 467-73.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
Abstract: E900
Type: Eposter Presentation
Background
Although recurrent chromosomal alterations are the main diagnostic and prognostic markers in acute myeloid leukemia (AML) at the time of diagnosis, nearly 50% of patients have an apparently normal karyotype (NKAML), displaying an intermediate risk for survival and relapse. SNP array (SNP-A) allow us to study variations in the number of copies (CNV) and regions of loss of heterozygozity (LOH) in myeloid neoplasms. Using systematically matched germline samples might ascertain the somatic nature of each lesion.
Aims
To establish the role that may play some cryptic abnormalities present in NKAML patients through the frequency, recurrence and any possible clinical association of CNVs and LOHs.
Methods
A total of 218 de novo NKAML patients were analyzed. Among them, 25 patients were enrolled in the consecutive multicenter PETHEMA trials at the Hospital Universitari i Politècnic La Fe and Hospital 12 de Octubre, with available DNA sample at diagnosis and at complete molecular remission were selected for this study. DNA from Hospital Universitari i Politècnic La Fe were provided by Biobank La Fe. We expanded the cohort with other AML series with publicly available SNP-A data to a total of 181 cases (n=49 del TCGA,a n=53 de Kronke J, et al.,b n=30 de Tadayuki A, et al.c y n=49 Koren-Michowitz M, et al.d). Samples were genotyped using Human CytoScan HD (n=37) and Genome-Wide Human SNP 6.0 (n=181) according to manufacturer’s protocol (Affymetrix Santa Clara, C.A., U.S.A.). DNA copy number and paired LOH analyses were performed using the Genotyping Console and the Chromosome Analyses Suite (ChAS) software (Affymetrix). Filters applied for segment Copy Number Abnormalities (CNA) detection were ≥20 consecutive markers in a region of at least 100Kb, and for regions of Copy Neutral Loss of Heterozygocity (CN-LOH), ≥100 markers in at least 500Kb. All abnormalities found in the remission sample were ruled out and assume as non-somatic. Besides, every potential abnormality was checked in the Database of Genomic Variants (http://projects.tcag.ca/variation). Size, position, and location of genes were identified with UCSC Genome Browser (http://genome.ucsc.edu/). The human reference sequence used for alignment was the GRCh37/hg19assembly
Results
A total of 304 abnormalities were found as an acquired event in 143 NKAML patients (66%), resulting in 2.1 abnormalities/case. These consisted of 151 heterozygous deletions, 99duplications and 54 CN-LOH. Cryptic chromosomal aberrations were more frequents in chr 1, 2, 5, 6, 7, 11, 13, 16 and 19. The most common CN-LOH was in 13q (being FLT3 involved in all them), 1p y 7p. In 19p (chr19:1-16300000) we detected more deletions, while in chr 1, 4, 5 and 20 more insertions. Likewise, patients harbored cryptic aberrations (mainly deletions or CN-LOH) involving KMT2A,(n=5), RAD21 (n=4), RUNX1 (n=4), ETV6 (n=3), EZH2 (n=3), WT1 (n=3), PTPN11 (n=2), TET2 (n=2), U2AF1 (n=2), IDH1 (n=1) and NPM1 (n=1). Further results will be presented.
Conclusion
This study has delineated recurrent abnormalities that may act as driver event and could explain leukemogenesis in up to 66% of NKAML cases. This work was supported by the following grants: Fundación Española de Hematología (FEHH), PI12/01047, RD12/0036/0014, PIE13/00046, PI13/01640, PI13/02837, PT13/0010/0026, PI14//01649 and PROMETEOII/2014/025a. N Engl J Med 2013; 368:2059–2074.b. Blood. 2013, 122 (1): 100-8.c. Haematologica. 2009, 94(2): 213-23.d. Leuk Res. 2012, 36(4): 467-73.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
Type: Eposter Presentation
Background
Although recurrent chromosomal alterations are the main diagnostic and prognostic markers in acute myeloid leukemia (AML) at the time of diagnosis, nearly 50% of patients have an apparently normal karyotype (NKAML), displaying an intermediate risk for survival and relapse. SNP array (SNP-A) allow us to study variations in the number of copies (CNV) and regions of loss of heterozygozity (LOH) in myeloid neoplasms. Using systematically matched germline samples might ascertain the somatic nature of each lesion.
Aims
To establish the role that may play some cryptic abnormalities present in NKAML patients through the frequency, recurrence and any possible clinical association of CNVs and LOHs.
Methods
A total of 218 de novo NKAML patients were analyzed. Among them, 25 patients were enrolled in the consecutive multicenter PETHEMA trials at the Hospital Universitari i Politècnic La Fe and Hospital 12 de Octubre, with available DNA sample at diagnosis and at complete molecular remission were selected for this study. DNA from Hospital Universitari i Politècnic La Fe were provided by Biobank La Fe. We expanded the cohort with other AML series with publicly available SNP-A data to a total of 181 cases (n=49 del TCGA,a n=53 de Kronke J, et al.,b n=30 de Tadayuki A, et al.c y n=49 Koren-Michowitz M, et al.d). Samples were genotyped using Human CytoScan HD (n=37) and Genome-Wide Human SNP 6.0 (n=181) according to manufacturer’s protocol (Affymetrix Santa Clara, C.A., U.S.A.). DNA copy number and paired LOH analyses were performed using the Genotyping Console and the Chromosome Analyses Suite (ChAS) software (Affymetrix). Filters applied for segment Copy Number Abnormalities (CNA) detection were ≥20 consecutive markers in a region of at least 100Kb, and for regions of Copy Neutral Loss of Heterozygocity (CN-LOH), ≥100 markers in at least 500Kb. All abnormalities found in the remission sample were ruled out and assume as non-somatic. Besides, every potential abnormality was checked in the Database of Genomic Variants (http://projects.tcag.ca/variation). Size, position, and location of genes were identified with UCSC Genome Browser (http://genome.ucsc.edu/). The human reference sequence used for alignment was the GRCh37/hg19assembly
Results
A total of 304 abnormalities were found as an acquired event in 143 NKAML patients (66%), resulting in 2.1 abnormalities/case. These consisted of 151 heterozygous deletions, 99duplications and 54 CN-LOH. Cryptic chromosomal aberrations were more frequents in chr 1, 2, 5, 6, 7, 11, 13, 16 and 19. The most common CN-LOH was in 13q (being FLT3 involved in all them), 1p y 7p. In 19p (chr19:1-16300000) we detected more deletions, while in chr 1, 4, 5 and 20 more insertions. Likewise, patients harbored cryptic aberrations (mainly deletions or CN-LOH) involving KMT2A,(n=5), RAD21 (n=4), RUNX1 (n=4), ETV6 (n=3), EZH2 (n=3), WT1 (n=3), PTPN11 (n=2), TET2 (n=2), U2AF1 (n=2), IDH1 (n=1) and NPM1 (n=1). Further results will be presented.
Conclusion
This study has delineated recurrent abnormalities that may act as driver event and could explain leukemogenesis in up to 66% of NKAML cases. This work was supported by the following grants: Fundación Española de Hematología (FEHH), PI12/01047, RD12/0036/0014, PIE13/00046, PI13/01640, PI13/02837, PT13/0010/0026, PI14//01649 and PROMETEOII/2014/025a. N Engl J Med 2013; 368:2059–2074.b. Blood. 2013, 122 (1): 100-8.c. Haematologica. 2009, 94(2): 213-23.d. Leuk Res. 2012, 36(4): 467-73.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
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