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This Week in Cell: Jun 27, 2018

Researchers from Dana-Farber Cancer Institute, the Broad Institute, Harvard Medical School, and other centers present structural variant profiles for advanced, metastatic prostate cancers, uncovering non-coding structural changes to seem to boost androgen receptor signaling in the cancers. Using the 10X Genomics linked-read sequencing platform, the team assessed tumor biopsy and matched germline samples from 23 metastatic castration-resistant prostate cancer cases, identifying haplotype resolved structural variants and rearrangements. Along with cell-free DNA profiles from 86 metastatic, advanced prostate cancer cases, the tumor sequences revealed rearrangements affecting new and known prostate cancer-related genes. As many as 87 percent of the tumors were marked by recurrent tandem duplications involving an androgen receptor (AR) enhancer region, for example, while AR and AR enhancer gains appeared to contribute to progression on treatment with drugs inhibiting the androgen pathway. GenomeWeb has more on this, here.

For a related Cell study, an international team led by another group at Dana-Farber and the Broad describe an AR enhancer that is somatically acquired in advanced prostate cancers, contributing to prostate cancer proliferation and therapeutic resistance. The researchers initially identified the suspicious somatically acquired AR enhancer — appearing as a DNaseI hypersensitivity peak — using available copy number profiles for 149 tumor samples from 60 men with castration-resistant prostate cancer. They subsequently characterized this site and its effects in more detail using a combination of chromatin immunoprecipitation sequencing, CRISPR-based genome editing, and epigenetic screening. From these and other findings, the authors say, "[w]e speculate that future efforts to target this enhancer may present additional viable opportunities for targeting the AR in advanced prostate cancer."

Finally, researchers from Caltech, the University of California, Los Angeles, the University of California, Riverside, and Stanford University introduce intron seqFISH, an in situ approach for visualizing burgeoning messenger RNA and long non-coding RNAs (lncRNAs) in individual cells. Using this multiplexed single-molecule imaging and immunofluorescence approach, the team tracked nascent transcription at 10,421 genes in mouse embryonic stem cells and fibroblasts, uncovering transcriptome dynamics over time and transcriptionally active loci at chromosome territory surfaces. "Together, spatial genomics of the nascent transcriptome by intron seqFISH reveals nuclear organizational principles and fast dynamics in single cells that are otherwise obscured," the authors write.