Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

Purpose: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies.

Transcriptome analysis of neural progenitor cells by a genetic dual reporter strategy.

Global analysis of stem/progenitor cells promises new insight into mechanisms that govern self-renewal and cellular potential, an unresolved question of stem/progenitor cell biology. Despite rapid advance of genome-wide profiling methods, the difficulty in cell purification remains a major challenge for global analysis of somatic stem/progenitor cells. Genetic tagging with a reporter provides a powerful tool for identification and isolation of a specific mature cell type; however, for stem/progenitor cells, reporter retention by progeny may be a concern for impurity.

Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs.

MicroRNAs (miRNAs) are 19-22-nucleotide noncoding RNAs that post-transcriptionally regulate mRNA targets. We have identified endogenous miRNA binding sites in mouse embryonic stem cells (mESCs), by performing photo-cross-linking immunoprecipitation using antibodies to Argonaute (Ago2) followed by deep sequencing of RNAs (CLIP-seq). We also performed CLIP-seq in Dicer⁻/⁻ mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA dependent.

Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.

miR-17 approximately 92, miR-106b approximately 25, and miR-106a approximately 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-1792 is observed in human cancers, and its oncogenic properties have been confirmed in a mouse model of B cell lymphoma. Here we show that mice deficient for miR-17 approximately 92 die shortly after birth with lung hypoplasia and a ventricular septal defect.