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This Week in Genome Research : Apr 25, 2018

A UK team takes a look at mutational signatures associated with DNA mismatch repair deficiency in the Caenorhabditis elegans worm model organism and in human tumor samples. The researchers used mutation accumulation assays and genome sequencing to follow the genetic alterations that accumulated in C. elegans worms missing the DNA mismatch repair genes PMS2 and MLH1 and/or the polymerase subunit-coding gene POLE4. One of the mutational signatures identified in the mismatch repair-deficient worms also turned up in the researchers' analysis of more than 500 colorectal or gastric adenocarcinoma samples, though the human tumor set contained two additional signatures suspected of stemming from more complex interactions between mismatch repair pathways and other mutation-causing processes.

Researchers from the UK, Norway, and Japan attempt to retrace transcription start site evolution in the human genome using a combination of functional data and an evolutionary analysis incorporating data for 10 non-human primates and half a dozen mammals outside of the primate lineages. With these types of data, the team considered roughly 200,000 human transcription start sites, clustering the sites based on their estimated evolutionary age. Along with factors affecting the advent of new transcription start sites, for example, the analysis provided a peek at the evolutionary trajectory and transcriptional activity associated with transcription start sites that formed relatively recently.

Finally, an Australian team tracks DNA methylation profiles in cancer-associated fibroblasts from the prostate cancer microenvironment. After culturing cancer-associated fibroblast and non-malignant prostate fibroblast cells from 17 men undergoing surgery for localized sporadic prostate cancer, the researchers used bisulfite sequencing to profile DNA methylation patterns in the cells, verifying these results with array-based methylation profiling. In the process, they saw DNA methylation shifts in the cancer-associated fibroblasts relative to the non-malignant prostate fibroblasts, particularly when it came to enhancer and promoter sequences. "Remarkably," they write, "a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment."