2 research outputs found
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics
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Importance of the Antarctic Slope Current in the Southern Ocean Response to Ice Sheet Melt and Wind Stress Change
We use two coupled climate models, GFDL-CM4 and GFDL-ESM4, to investigate the physical response of the Southern Ocean to changes in surface wind stress, Antarctic meltwater, and the combined forcing of the two in a pre-industrial control simulation. The meltwater cools the ocean surface in all regions except the Weddell Sea, where the wind stress warms the near-surface layer. The limited sensitivity of the Weddell Sea surface layer to the meltwater is due to the spatial distribution of the meltwater fluxes, regional bathymetry, and large-scale circulation patterns. The meltwater forcing dominates the Antarctic shelf response and the models yield strikingly different responses along West Antarctica. The disagreement is attributable to the mean-state representation and meltwater-driven acceleration of the Antarctic Slope Current (ASC). In CM4, the meltwater is efficiently trapped on the shelf by a well resolved, strong, and accelerating ASC which isolates the West Antarctic shelf from warm offshore waters, leading to strong subsurface cooling. In ESM4, a weaker and diffuse ASC allows more meltwater to escape to the open ocean, the West Antarctic shelf does not become isolated, and instead strong subsurface warming occurs. The CM4 results suggest a possible negative feedback mechanism that acts to limit future melting, while the ESM4 results suggest a possible positive feedback mechanism that acts to accelerate melt. Our results demonstrate the strong influence the ASC has on governing changes along the shelf, highlighting the importance of coupling interactive ice sheet models to ocean models that can resolve these dynamical processes. © 2022. American Geophysical Union. All Rights Reserved.6 month embargo; first published: 28 April 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]