Showing papers by "Jay Bowen published in 2018"
TL;DR: Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, Pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which may inform strategies for future therapeutic development.
1,535 citations
TL;DR: The genomic and phenotypic correlates of cancer aneuploidy are defined and genome engineering is applied to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication.
660 citations
TL;DR: In this article, the authors made two errors in preparation of this manuscript and corrected them in the revised Figure S7 by re-ordering the mutations by frequency for COAD and READ independently.
303 citations
TL;DR: expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling, and chromatin, translation, and DNA replication/repair were conserved pan-cancer, suggesting that MYC is a distinct oncogenic driver.
Abstract: 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.
248 citations
Joshua D. Campbell1, Joshua D. Campbell2, Joshua D. Campbell3, Christina Yau4 +766 more•Institutions (23)
TL;DR: This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas from five sites associated with smoking and/or human papillomavirus.
234 citations
TL;DR: A molecular link between thymoma and the autoimmune disease myasthenia gravis is identified, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.
222 citations
TL;DR: An integromic analysis of gene alterations that modulate transforming growth factor β-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily.
Abstract: We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily.
115 citations