Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.
Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression.
The Arabidopsis Information Resource (TAIR, http://arabidopsis.org) is a genome database for Arabidopsis thaliana, an important reference organism for many fundamental aspects of biology as well as basic and applied plant biology research. TAIR serves as a central access point for Arabidopsis data, annotates gene function and expression patterns using controlled vocabulary terms, and maintains and updates the A. thaliana genome assembly and annotation. TAIR also provides researchers with an extensive set of visualization and analysis tools. Recent developments include several new genome releases (TAIR8, TAIR9 and TAIR10) in which the A. thaliana assembly was updated, pseudogenes and transposon genes were re-annotated, and new data from proteomics and next generation transcriptome sequencing were incorporated into gene models and splice variants. Other highlights include progress on functional annotation of the genome and the release of several new tools including Textpresso for Arabidopsis which provides the capability to carry out full text searches on a large body of research literature.
The Arabidopsis Information Resource (TAIR, http://arabidopsis.org) is the model organism database for the fully sequenced and intensively studied model plant Arabidopsis thaliana. Data in TAIR is derived in large part from manual curation of the Arabidopsis research literature and direct submissions from the research community. New developments at TAIR include the addition of the GBrowse genome viewer to the TAIR site, a redesigned home page, navigation structure and portal pages to make the site more intuitive and easier to use, the launch of several TAIR web services and a new genome annotation release (TAIR7) in April 2007. A combination of manual and computational methods were used to generate this release, which contains 27 029 protein-coding genes, 3889 pseudogenes or transposable elements and 1123 ncRNAs (32 041 genes in all, 37 019 gene models). A total of 681 new genes and 1002 new splice variants were added. Overall, 10 098 loci (one-third of all loci from the previous TAIR6 release) were updated for the TAIR7 release.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.