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Study Offers Insights Into Role of Structural Variants in Cancer

Combining genomic profiling and genome engineering, a team led by the Salk Institute for Biological Studies' Jesse Dixon has uncovered new details about how some structural variants (SVs) can activate oncogenes to promote cancer. SVs that alter three-dimensional genome organization can lead to enhancer-promoter rewiring and human disease, particularly cancer. But only a small number of SVs are associated with altered gene expression and it is not known why only certain SVs lead to changes in distal gene expression. To investigate, the scientists analyzed Hi-C sequencing data from 92 cancer cell lines and patient samples, finding loci affected by recurrent alterations to 3D genome structure including important oncogenes. As reported in Nature this week, they then used CRISPR/Cas9 genome editing to generate de novo SVs in cell lines and show that oncogene activity can be predicted by using models that consider partner region chromatin contacts and enhancer activity. "Critically, the expression of only a subset of genes is sensitive to these engineered rearrangements, and we observe that only a minority of genes in the genome show evidence of responsiveness to changes in their local enhancer landscape," the study's authors write. "These results indicate that alterations to gene regulatory 3D architecture are a critical mechanism that enables oncogene activation in cancer genomes and sheds light on the essential elements for such gene activation events.

The Scan

Study Links Evolution of Longevity, Social Organization in Mammals

With the help of comparative phylogenetics and transcriptomics, researchers in Nature Communications see ties between lifespan and social organization in mammals.

Tumor Microenvironment Immune Score Provides Immunotherapy Response, Prognostic Insights

Using multiple in situ analyses and RNA sequence data, researchers in eBioMedicine have developed a score associated with immunotherapy response or survival.

CRISPR-Based Method for Finding Cancer-Associated Exosomal MicroRNAs in Blood

A team from China presents in ACS Sensors a liposome-mediated membrane fusion strategy for detecting miRNAs carried in exosomes in the blood with a CRISPR-mediated reporter system.

Drug Response Variants May Be Distinct in Somatic, Germline Samples

Based on variants from across 21 drug response genes, researchers in The Pharmacogenomics Journal suspect that tumor-only DNA sequences may miss drug response clues found in the germline.