Researchers from the University of California, San Francisco, Washington University in St. Louis, and elsewhere characterize structural variants affecting regulatory loci in more than 100 metastatic, castration-resistant prostate cancers. The team did deep whole-genome sequencing and RNA sequencing on matched tumor and normal samples from 101 individuals with castration-resistant prostate cancer, focusing on metastases from the bone, lymph node, liver, or other soft tissue sites. Along with recurrent amplifications upstream of the androgen receptor (AR) gene, which enhanced its expression in more than 80 percent of the patients, the investigators detected tandem duplications influencing AR or MYC regulation and uncovered ties between specific structural variation types and mutations involving DNA repair genes such as CDK12, TP53, or BRCA2.
A University of Oulu-led team takes a look at the consequences of a chromosome 19 SNP linked to aggressive prostate cancer through past genome-wide association studies. The researchers verified the variant's association with prostate cancer aggressiveness and prognoses using array-based germline genotyping profiles for 2,738 prostate cancer patients from Finland, before delving into the expression effects of the risky rs11672691 variant in normal prostate and prostate cancer cell lines with RNA sequencing, chromatin immunoprecipitation sequencing, and other approaches. In particular, their results point to ties between the prostate cancer-associated version of rs11672691 and expression of genes such as PCAT19 and CEACAM21, in part by influencing binding patterns for a cancer-related transcription factor called HOXA2.
GenomeWeb has more on both those studies, here.
Finally, researchers from the Memorial Sloan Kettering Cancer Center, Columbia University, and other centers explore immune features in the breast cancer microenvironment using a combination of single-cell RNA sequencing, computational analyses, and T cell receptor (TCR) sequencing. The team did single-cell RNA-seq on some 47,000 CD45+ immune cells from eight treatment-naïve breast carcinoma cases, along with cells from matched normal breast, blood, and lymph node samples. With a computational pipeline called Biscuit, the authors saw immune cell expansions and co-expression patterns in the tumor microenvironment, using TCR sequencing to further characterize the T cell populations at play in this process. "Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer," the authors report.