Project description:Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.

2022-10-04 | GSE147123 | GEO

Integrative Analysis of Pathogenic Structural Variants in Leukemia Genomes

Project description:Pathogenic Structural Variants in Leukemia Genomes

| PRJEB50975 | ENA

Linked-Read Sequencing to Resolve Complex Structural Variants

Project description:Linked-Read Sequencing to Resolve Complex Structural Variants

| PRJNA516493 | ENA

Linked-Read Sequencing to Resolve Complex Structural Variants

Project description:Linked-Read Sequencing to Resolve Complex Structural Variants

| PRJNA516494 | ENA

Expression data from leukemic patients with complex structural variants

Project description:Expression data from leukemic patients with complex structural variants

| PRJNA511661 | ENA

Structural variants drive context dependent oncogene activation in cancer

Project description:Structural variants drive context dependent oncogene activation in cancer

| PRJNA613064 | ENA

Somatically Acquired Structural Genetic Differences; a Longitudinal Study of Elderly Danish Twins

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

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