Illumina and Affymetrix SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25117 | GEO | 2012/07/03
SECONDARY ACCESSION(S): PRJNA134513
REPOSITORIES: GEO
Similar Datasets
Project description:Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.
2012-07-03 | GSE25102 | GEO
Project description:Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.
2012-07-03 | GSE25116 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE25102: Illumina SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples GSE25116: Affymetrix SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples Refer to individual Series
2012-07-02 | E-GEOD-25117 | biostudies-arrayexpress
Project description:Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL. Illumina SNP-array genotyping was performed according to the manufacturer's directions on DNA extracted from 2 leukemic bone marrow samples and two corresponding normal blood samples. The genotype data from the arrays were used for quality assesment of genotype data from high throughput sequencing.
2012-07-02 | E-GEOD-25102 | biostudies-arrayexpress
Project description:Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 2 leukemic bone marrow samples and two corresponding normal blood samples.
2012-07-02 | E-GEOD-25116 | biostudies-arrayexpress
Project description:UnlabelledBackgroundAcute lymphoblastic leukemia (ALL) is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21) translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL) patients.Result155 chromosomal aberrations (119 losses, 36 gains) were reported in the array findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6 gene deletion occurred in 4 of the patients, corresponding to 45% of the sample. The most common alterations above 1 Mb were deletion 6q (13%), 12p (12%) and 9p (8%), and duplication 4q (6%) and Xq (4%). Other genes important in ALL were also identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH technique was able to detect microdeletion as small as 400 bp.ConclusionThe results demonstrate the usefulness of high resolution array-CGH as a complementary tool in the investigation of ALL.
| S-EPMC3549777 | biostudies-literature
Project description:ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N=36), XIIIB (N=38) and XV (N=94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P<0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P=0.04; 5-year estimate, 96.8±2.4% versus 88.3±2.5%) and OS (P=0.04; 98.9±1.4% versus 93.7±1.8%) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P=0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.
| S-EPMC3345278 | biostudies-literature
Project description:The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q), and +16 as possible early events in the leukemogenic process.
2010-07-07 | GSE19996 | GEO
Project description:In precursor B-cell acute lymphoblastic leukemia (ALL), whole chromosome uniparental isodisomy (wUPD) occurs almost uniquely in the high hyperdiploid (51-67 chromosomes) (HH) subtype. Comparison of 26 HH with wUPD with 31 with noUPD, showed a higher modal number of chromosomes and gains of 5+ in wUPD. Mutations in genes within epigenetic pathways with upregulation of genes involved in cellular response to stress and stimuli, and mutations in RAS/RTK pathways and upregulation of genes in RNA Polymerase III pathway were seen in wUPD and noUPD respectively. Though overall outcomes were similar in patient with and without wUPD, those with noUPD were more likely to have residual disease after treatment. Differential gene expression between the two groups showed upregulation of genes involved in thiopurine drug resistance in wUPD. Genome-wide differences between HH ALL with and without UPD identified plausible biological explanations for the heterogeneity in therapeutic response in HH ALL.
2023-09-30 | GSE197838 | GEO
Project description:Ibrutinib (Ibr), an orally administered covalent inhibitor of Bruton’s kinase, has generated remarkable responses in CLL patients including those with an unfavorable cytogenetic profile. Once patients develop resistance to ibrutinib, the outcome is poor with few treatment options. To further understand the genomic mechanisms underlying Ibr resistance, we’ve performed genome wide copy number analysis of serial samples collected from nine ibrutinib-relapsed patients. Deletions of 18p often coincide with del(17p)/TP53 mutations, predispose patients to relapse.
2017-04-06 | GSE97436 | GEO