Ad616dc2-c344-4b80-87f5-7d1579da46e6 - samples
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ABSTRACT:
PROVIDER: EGAD00001004838 | EGA |
REPOSITORIES: EGA
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Project description:Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults.
2015-07-30 | GSE67271 | GEO
Project description:The lack of prognostic biomarkers and therapeutic targets in triple-negative breast cancer (TNBC) underscores an urgent need for the identification of novel biomarkers and effective treatment targets. In this study, we collected tumor and adjacent normal samples of four TNBC and four non-TNBC patients for whole-exome sequencing (WES).Comparative WES analysis uncovered the distinct landscape of somatic mutations and driver genes in TNBC.
2025-10-07 | GSE267443 | GEO
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE117692 | GEO
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE116057 | GEO
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE117693 | GEO
Project description:Background and Aims: Evidence for a genetic contribution to eosinophilic esophagitis (EoE) exists from family and genome-wide association studies. Extensive investigation into rare variants contributing to EoE has not been performed. The Aim is to evaluate families with multiple cases of EoE by genomic and transcriptomic sequencing to identify genes predisposing to EoE. Methods: We whole exome sequenced (WES) distant relative pairs (e.g., cousins) in extended EoE pedigrees and other affected relatives to identify rare, shared, potentially pathologic variants. Whole-transcriptome sequencing by RNA-Seq was performed in nuclear families with multiple EoE cases. We compared the overlap of genes from DNA and RNA sequencing for relevance to disease manifestations. Results: WES was performed in 50 familial cases in 21 EoE extended pedigrees. We observed 219 rare, candidate predisposition variants in 210 genes with complete sharing among all affected family members. Transcriptome sequencing was performed for 43 EoE cases in 18 nuclear kindreds, including 6 relatives without EoE. We observed 10,070 total differentially expressed genes compared to controls. We identified three genes (MUC16, ADGRE1, and TENM3) with evidence of rare variant sharing and differential gene expression among all affected family members. We identified 43 other genes with partial sharing of rare variants among affected family members and with differential gene expression. Several genes identified as prominent in EoE were also differentially expressed in unaffected relatives. Conclusions: Multiple genes related to immune response, barrier dysfunction, and cell adhesion were identified in familial EoE cases and unaffected family members supporting a genetic familial predisposition and a possible multi-hit background to disease pathophysiology.
2025-01-24 | GSE250595 | GEO
Project description:Within the frame of inherited cancer predisposition, single gene carriers of pathogenic variants (PVs) have been extensively represented in the literature, whereas the oligogenic coinheritance of heterozygous PVs in cancer-related genes is a poorly studied event. Currently, due to the increment of cancer survivors, the probability of presenting multiple primary cancers (MPC) is higher. This study included MPC patients ≤45 years without known PVs in common cancer predisposition genes. We used whole exome sequencing (WES) of germline and tumoral DNA, chromosomal microarray analysis (CMA) on germline DNA (patient 1-7, and patient 9-10), and karyotype of patient 8to detect variants associated with the disease. The ten patients included in the study presented a mean of 3 cancers per patient. CMA showed two microduplications and one microdeletion, while WES of the germline DNA identified 1-3 single nucleotide variants of potential interest to the disease in each patient and two additional copy number variants. Most of the identified variants were classified as variants of uncertain significance. The mapping of the germline variants into their pathways showed a possible additive effect of these as the cause of the cancer. Twelve somatic samples from 5 patients were available for sequencing. All the germline variants were also present in the somatic samples, while no second hits were identified in the same genes. The sequencing of patients with early cancers, family history and multiple tumors is already a standard of care. However, the growing evidence suggests that patient´s assessment should not stop at the identification of one PV in a cancer predisposition gene.
2024-08-29 | GSE271498 | GEO
Project description:Sequence-based genetic testing identifies causative variants in ~50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.
2024-06-13 | GSE269416 | GEO
Project description:CD20 protein-negative diseases were observed for a subset of patients with B-NHL that relapsed after initial responses to mosunetuzumab. For many of these tumors, whole exome (WES) and RNA-seq failed to detect any MS4A1 genetic variants or loss of CD20 mRNA, which could have explained the apparent loss of CD20 protein. For this study, we obtained formalin-fixed paraffin-embedded (FFPE) tumor samples from a similar cohort of four additional patients relapsing after mosunetuzumab, and performed RNA-seq to look for changes in the splicing pattern of CD20.
2023-12-08 | GSE243919 | GEO
Project description:Germline heterozygous GATA2 mutations cause GATA2 deficiency, a complex disorder characterized by bone marrow failure, immunodeficiency, and a high risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The disease evolves variably among patients, leading to anxiety for families. Due to phenotypic diversity and clinical overlap, timely diagnosis is often challenging. GATA2 carriers exhibit variable expressivity, with some developing early-onset MDS while others remain asymptomatic, suggesting that genetic and epigenetic factors influence disease progression. While advances in diagnostics through whole-exome sequencing (WES) and whole genome sequencing (WGS) have been made, few epigenetic studies have focused on GATA-related MDS. We present a familial case of four GATA2 carriers, two of whom are asymptomatic and two have developed MDS. Notably, we conducted a longitudinal epigenome analysis of one patient, tracking progression from asymptomatic to MDS, providing key insights with potential clinical applications
2025-04-16 | GSE280776 | GEO