Todd R. Golub

TL;DR: It is suggested that Lenalidomide-responsive patients without 5q deletions have a defect in erythroid differentiation analogous to the ineffective erythropoiesis in patients with 5Q deletions, and that an erythyroid gene expression signature predicts Lenalidumide activity in MDS.

Abstract: We previously reported the genomic evolution of the copy number (CN) landscapes of patient-derived xenografts (PDXs) during their engraftment and passaging1. Woo et al. argue that the CN profiles of PDXs are highly conserved, and that the main conclusions of our paper are invalid due to our use of expression-based CN profiles2. Here, we reassess genomic evolution of PDXs using the DNA-based CN profiles reported by Woo et al. We find that the degree of genomic evolution in the DNA-based dataset of Woo et al. is similar to that which we had previously reported. While the overall Pearson’s correlation of CN profiles between primary tumors (PTs) and their derived PDXs is high (as reported in our original paper as well), a median of ~10% of the genome is differentially altered between PTs and PDXs across cohorts (range, 0% to 73% across all models). In 24% of the matched PT-PDX samples, over a quarter of the genome is differentially affected by CN alterations. Moreover, in matched analyses of PTs and their derived PDXs at multiple passages, later-passage PDXs are significantly less similar to their parental PTs than earlier-passage PDXs, indicative of genomic divergence. We conclude that genomic evolution of PDX models during model generation and propagation should not be dismissed, and that the phenotypic consequences of this evolution ought to be assessed in order to optimize the application of these valuable cancer models.

TL;DR: Crompton et al. as mentioned in this paper performed whole-exome sequencing of 96 Ewing sarcoma tumors and 11 Ewing SARcoma cell lines, as well as whole-genome sequencing, transcriptome sequencing and copy-number analysis of a subset of these samples.

TL;DR: Tabrizi et al. as discussed by the authors used an intravenous DNA-binding priming agent that is given 2 hours prior to a blood draw to recover more ctDNA, boosting the detection of tumor mutations in plasma by 19-fold and increasing sensitivity from 6% to 84.