The trial will also provide evidence on the feasibility of the approach of addressing distal and proximate drivers of vulnerability among adolescent girls in this setting.
We assessed the drivers of the distal 16p11.2 duplication by overexpressing each of the nine encompassed genes in zebrafish.
ZNF703 has been demonstrated, with high likelihood, to be the principle oncogenic driver of the distal A1 core [ 45, 46], resulting in induction of stem-cell-like phenotypes, potentially also suppressing ER and promoting E2F1 transcriptional activity [ 47].
In this study, we profiled two cohorts of 171 and 1001 primary breast cancers to further refine the minimal amplicon, and have functionally characterized ZNF703, the sole candidate that emerged from these studies, as the likely driver oncogene at distal 8p12.
All of these observations provide compelling evidence to support ZNF703 as the driver oncogene of the distal 8p12 amplicon.
Since the network topology is undirected, local eQTL effects on nonhub driver genes may lead to spurious distal associations in the analysis.
Here, we characterize ZNF703 as the driver of the frequent amplification of a distal 8p12 locus, which occurs in around 1/3 of Luminal B breast cancers, less frequently in other ER-positive tumours and uncommonly in ER-negative tumours.
We refer to the combination of distal cis-regulatory ("enhancers") and basal promoter elements as the "driver".
Layer 6 terminals in the thalamus are small, innervate distal dendrites via single synapses, and do not represent a driver input (Reichova and Sherman 2004).
As GlyRS was observed in the axonal bundles, we expressed both GlyRSWT and GlyRSP234KY using a neuronal-specific driver (elav-GAL4) to determine whether GlyRS reaches the most distal region of the motor neuron, the NMJ (Fig. 1C and D).
