Volume 52 Issue 7, 2 July 2020

How ‘difficult’ is it for somatic evolution to produce a cell that is capable of leaving the primary tumor and growing in a distant organ? In this issue, Reiter et al. assess genetic diversity across metastatic lesions and identify a tight selective bottleneck preceding distant metastasis.

Pachytene Piwi-interacting RNAs (piRNAs) are abundant small non-coding RNAs expressed in mammalian germ lines. A new study indicates that, among the diverse pool of piRNA sequences, a small number act as highly selective guides that induce cleavage of coding and non-coding transcripts, thus promoting piRNA generation and regulating gene expression.

This review discusses major privacy threats relevant to collection and analysis of genomic data in the context of direct-to-consumer applications and provides suggestions for improving the design of privacy-protecting approaches.

CTCF is dispensable for transdifferentiation of B cells into induced macrophages despite widespread loss of topologically associating domains. CTCF depletion impairs upregulation of inflammatory genes after endotoxin exposure by destabilizing promoter–enhancer interactions.

Cas9 expression induces DNA damage and activates the p53 pathway, and it can lead to the selection of cells with p53-inactivating mutations. Cas9 is less active in wild-type TP53 cell lines than in TP53-mutant cell lines.

Genome-wide analysis in 212,453 Japanese individuals identifies loci associated with 42 diseases. Comparative analysis with European populations identifies East Asian–specific associations.

Genome-wide association meta-analyses among 1.4 million individuals identify 318 new risk loci for type 2 diabetes and provide insight into the contribution of these risk variants to diabetes-related vascular outcomes.

Analysis of metastases using a mathematical framework and multi-region sampling data shows that lymph node metastases have higher levels of intratumor heterogeneity than distant metastases, and that these form via different evolutionary mechanisms.

Analysis of whole-exome sequencing data from paired primary tumors and metastases from patients with breast, colorectal and lung cancer identifies clonal remodeling associated with therapy and few metastasis-private clonal mutations, consistent with early metastatic seeding.

Longitudinal single-cell analysis of transcription and DNA methylation dynamics in cancer cell lines suggests a clonally stable epigenetic memory. Colon cancer cells show a spectrum of epithelial-to-mesenchymal identities that seems independent of genetic variation.

Analysis with alleles encoding pharmacologically degradable Mediator subunits shows that Mediator acts as a global coactivator that facilitates transcription globally but is acutely required for cell-type-specific gene regulatory circuits.

Male mice lacking piRNAs from a conserved locus on chromosome 6 (pi6) produce sperm with defects in capacitation and egg fertilization. pi6 piRNAs repress mRNAs required for sperm function.

CAUSE is a new Mendelian randomization method that accounts for correlated and uncorrelated horizontal pleiotropic effects. CAUSE is more robust to correlated pleiotropy than other methods and avoids identifying unlikely causal relationships.