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

Late‐stage calcites in the Permian Capitan Formation and its equivalents, Delaware Basin margin, west Texas and New Mexico: evidence for replacement of precursor evaporites

Comparison of Upper Guadalupian fore‐reef, reef and back‐reef strata from outcrops in the Guadalupe Mountains with equivalent subsurface cores from the northern and eastern margins of the Delaware Basin indicates that extensive evaporite diagenesis has occurred in both areas. In both surface and subsurface sections, the original sediments were extensively dolomitized and most primary and secondary porosity was filled with anhydrite. These evaporites were emplaced by reflux of evaporitic fluids from shelf settings through solution‐enlarged fractures and karstic sink holes into the underlying strata. Outcrop areas today, however, contain no preserved evaporites in reef and fore‐reef sections and only partial remnants of evaporites are retained in back‐reef settings. In their place, these rocks contain minor silica, very large volumes of coarse sparry calcite and some secondary porosity. The replacement minerals locally form pseudomorphs of their evaporite precursors and, less commonly, contain solid anhydrite inclusions. Some silicification, dissolution of anhydrite and conversion of anhydrite to gypsum have occurred in these strata where they are still buried at depths in excess of 1 km; however, no calcite replacements were noted from any subsurface core samples. Subsurface alteration has also led to the widespread, late‐stage development of large‐ and small‐scale dissolution breccias. The restriction of calcite cements to very near‐surface sections, petrographic evidence that the calcites post‐date hydrocarbon emplacement, and the highly variable but generally ‘light’carbon and oxygen isotopic signatures of the spars all indicate that calcite precipitation is a very late diagenetic (telogenetic) phenomenon. Evaporite dissolution and calcitization reactions have only taken place where Permian strata were flushed with meteoric fluids as a consequence of Tertiary uplift, tilting and breaching of regional hydrological seals. A typical sequence of alteration involves initial corrosion of anhydrite, one or more stage

Diffraction determination of stress field and elastic constants in polycrystalline materials

(Cell 173, 371\u2013385.e1\u2013e9; April 5, 2018) It has come to our attention that we made two errors in preparation of this manuscript. First, in the STAR Methods, under the subheading of \u201cHypermutators and Immune Infiltrates\u201d within the \u201cQuantification and Statistical Analysis\u201d section, we inadvertently referred to Figures S7A\u2013S7C for data corresponding to sample stratification by hypermutator status alone in the last sentence. It should have referred to Figure S6A\u2013S6C. Second, the lists of highly frequent missense mutations for COAD (colon adenocarcinoma) and READ (rectum adenocarcinoma) displayed in Figure S7 were incorrect because when we ordered the mutations in the initial analysis, we mistakenly combined the two cancer types COAD and READ for analysis, despite the fact that they were listed as two separate cancer types in the x-axis of the figure. After re-ordering the mutations by frequency for COAD and READ independently, information on highly frequent missense mutations for each of these cancer types is different and updated now in the revised Figure S7. These errors don't change the major conclusions of the paper and have been corrected online. We apologize for any confusion they may have caused. [Figure-presented