Acquired somatic variants in inherited myeloid malignancies
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB49554 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR7782690_1.fastq.gz | Fastqsanger.gz | |||
| ERR7782690_2.fastq.gz | Fastqsanger.gz | |||
| ERR7782700_1.fastq.gz | Fastqsanger.gz | |||
| ERR7782700_2.fastq.gz | Fastqsanger.gz | |||
| ERR7782710_1.fastq.gz | Fastqsanger.gz |
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| S-EPMC9061295 | biostudies-literature
Project description:Single nucleotide variants (SNVs) in regulatory DNA are linked to inherited cancer risk. Massively parallel reporter assays (MPRA) of 5,031 SNVs linked to 14 neoplasms comprising >90% of human malignancies were performed in pertinent diploid cell types then integrated with matching chromatin accessibility, looping, and eQTL data to identify 411 regulatory SNVs and their putative target eGenes. The latter highlighted specific protein networks in lifetime cancer risk, including mitochondrial translation, proliferation, signaling, adhesion, and immunity. This cancer SNV compendium underscores the importance of studying pathogenic variants in disease-relevant cells and implicates specific dysregulated gene networks in cancer predisposition. It also indicates that inherited cancer risk can impact the same gene via orthogonal genetic mechanisms of dysregulated expression as well as protein coding sequence alteration and demonstrates that a subset of germline-encoded risk genes also enable tumor growth of established cancers.
2024-08-22 | GSE183348 | GEO
Project description:Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested that they may accumulate in elderly individuals. To further explore the presence and the age-related acquisition of somatic structural variants in the human genome, we investigated CNVs acquired over a period of 10 years in 86 elderly Danish twins as well as CNV discordances between co-twins of 18 monozygotic twin pairs. Furthermore, the presence of mosaic structural variants was explored.
2016-06-23 | GSE76390 | GEO
Project description:Single nucleotide variants (SNVs) in regulatory DNA are linked to inherited cancer risk. Massively parallel reporter assays (MPRA) of 5,031 SNVs linked to 14 neoplasms comprising >90% of human malignancies were performed in pertinent diploid cell types then integrated with matching chromatin accessibility, looping, and eQTL data to identify 411 regulatory SNVs and their putative target eGenes. The latter highlighted specific protein networks in lifetime cancer risk, including mitochondrial translation, proliferation, signaling, adhesion, and immunity. This cancer SNV compendium underscores the importance of studying pathogenic variants in disease-relevant cells and implicates specific dysregulated gene networks in cancer predisposition. It also indicates that inherited cancer risk can impact the same gene via orthogonal genetic mechanisms of dysregulated expression as well as protein coding sequence alteration and demonstrates that a subset of germline-encoded risk genes also enable tumor growth of established cancers.
2024-08-22 | GSE183301 | GEO
Project description:Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1 % of ESR1-positive breast cancers2â5, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer riskâassociated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. RNA-Seq was performed in HCC1419 cells heterozygous for the functional SNV, rs9383590, to determine which genes displayed an allelic imbalance within a 1MB window.
2016-08-23 | E-GEOD-74718 | biostudies-arrayexpress
Project description:Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1 % of ESR1-positive breast cancers2–5, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk–associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer.
2016-08-23 | GSE74718 | GEO
Project description:Inherited functional regulatory risk variants for common human cancers
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Project description:Cell transplantation strategies for acquired and inherited disorders of peripheral myelin
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Project description:Thousands of noncoding somatic Single Nucleotide Variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes, reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1 and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators’ tumor cistromes, exemplified at the 8q24 locus harboring both risk-variants and somatic SNVs in cis-regulatory elements, upregulating MYC expression and altering the binding of transcription regulators to DNA. However, Massively-Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual CREs. Instead, SNVs accumulate, similarly to inherited riskvariants, in cistromes of master transcription regulators required for prostate cancer development. Significance Difficulties in inferring the biological significance of noncoding mutations have limited their inclusion in precision genomics medicine pipelines. Most attempts to delineate a role for noncoding mutations relied on detecting evidence for positive selection within individual CREs, such as reported for the TERT gene promoter. By considering the enrichment of noncoding mutations in cistromes as opposed to individual CREs, we reveal their specificity towards master transcription regulators that promote prostate cancer development, a feature shared with inherited risk-variants. Overall, our work provides a blueprint for the functional interpretation of noncoding mutations in genomic tests relying on defining cis-regulatory units according to cistrome-partitioning to identify cancer driver transcription regulators.
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Project description:At least six histone H1 variants exist in mammalian somatic cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be involved in the active regulation of gene expression. It is not well known whether the different variants have specific roles, are distributed differentially along the genome, or regulate specific promoters. By taking advantage of specific antibodies to H1 variants and HA-tagged recombinant H1 variants expressed in a breast cancer-derived cell line, we have investigated the distribution of the different somatic H1 variants (H1.2 to H1.5, H1.0 and H1X) in particular promoters and genome-wide. Genome-wide analysis of H1.0, H1.2, H1.4, H1X and H3
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