Abstract:
:Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of 3508 exons from 577 cancer-related genes using next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, and 13q14.12. Key genes mapping within these deleted regions include PTEN, BRCA2, C13ORF15, and SIAH3. Focal high-level amplifications were detected at 5p13.2-p12, 14q21.1, 7q22.1, and Xq12. Key amplified genes mapping within these regions include SKP2, FOXA1, and AR. Furthermore, targeted mutational analysis of normal-tumor pairs has identified somatic mutations in genes known to be associated with prostate cancer including AR and TP53, but has also revealed novel somatic point mutations in genes including MTOR, BRCA2, ARHGEF12, and CHD5. Finally, in one patient where multiple independent metastatic tumors were available, we show common and divergent somatic alterations that occur at both the copy number and point mutation level, supporting a model for a common clonal progenitor with metastatic tumor-specific divergence. Our study represents a deep genomic analysis of advanced metastatic prostate tumors and has revealed candidate somatic alterations, possibly contributing to lethal prostate cancer.
journal_name
Genome Resjournal_title
Genome researchauthors
Robbins CM,Tembe WA,Baker A,Sinari S,Moses TY,Beckstrom-Sternberg S,Beckstrom-Sternberg J,Barrett M,Long J,Chinnaiyan A,Lowey J,Suh E,Pearson JV,Craig DW,Agus DB,Pienta KJ,Carpten JDdoi
10.1101/gr.107961.110subject
Has Abstractpub_date
2011-01-01 00:00:00pages
47-55issue
1eissn
1088-9051issn
1549-5469pii
gr.107961.110journal_volume
21pub_type
杂志文章相关文献
GENOME RESEARCH文献大全abstract::Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation of oncogenes to the tumorigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.109678.110
更新日期:2011-04-01 00:00:00
abstract::DNA microarrays produced by deposition (or 'spotting')of a single long oligonucleotide probe for each gene may be an attractive alternative to other types of arrays. We produced spotted oligonucleotide arrays using two large collections of approximately 70-mer probes, and used these arrays to analyze gene expression i...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.1048803
更新日期:2003-07-01 00:00:00
abstract::Giardia duodenalis is the best-characterized example of the most ancient eukaryotes, which are primitively amitochondrial and anaerobic. The surface of Giardia is coated with cysteine-rich proteins. One family of these proteins, CRP136, varies among isolates and upon environmental stress. A repeat region within the CR...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.7.1.37
更新日期:1997-01-01 00:00:00
abstract::Animal microRNA sequences are subject to 3' nucleotide addition. Through detailed analysis of deep-sequenced short RNA data sets, we show adenylation and uridylation of miRNA is globally present and conserved across Drosophila and vertebrates. To better understand 3' adenylation function, we deep-sequenced RNA after k...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.106054.110
更新日期:2010-10-01 00:00:00
abstract::Establishment of spatial coordinates during Drosophila embryogenesis relies on differential regulatory activity of axis patterning enhancers. Concentration gradients of activator and repressor transcription factors (TFs) provide positional information to each enhancer, which in turn promotes transcription of a target ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.242362.118
更新日期:2019-05-01 00:00:00
abstract::Chromosome 21 represents approximately 1% of the human genome, and its long arm has been estimated to contain 600-1000 genes. A dense linkage map and almost complete physical maps based on yeast artificial chromosomes (YACs) and cosmids have been developed. We have used exon trapping to identify portions of genes from...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6.8.747
更新日期:1996-08-01 00:00:00
abstract::In comparison to genotypes, knowledge about haplotypes (the combination of alleles present on a single chromosome) is much more useful for whole-genome association studies and for making inferences about human evolutionary history. Haplotypes are typically inferred from population genotype data using computational met...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.077065.108
更新日期:2008-08-01 00:00:00
abstract::We developed a microarray platform for PCR amplification-independent expression profiling of minute samples. A novel scanning system combined with specialized biochips enables detection down to individual fluorescent oligonucleotide molecules specifically hybridized to their complementary sequence over the entire bioc...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.4999906
更新日期:2006-08-01 00:00:00
abstract::Changes in gene order between the genomes of two related yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus var. uvarum were studied. From the dataset of a previous low coverage sequencing of the S. bayanus var. uvarum genome, 35 different synteny breakpoints between neighboring genes and two cases of l...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.212701
更新日期:2001-12-01 00:00:00
abstract::The capacity of the honey bee to produce three phenotypically distinct organisms (two female castes; queens and sterile workers, and haploid male drones) from one genotype represents one of the most remarkable examples of developmental plasticity in any phylum. The queen-worker morphological and reproductive divide is...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.236497.118
更新日期:2018-10-01 00:00:00
abstract::Theory is developed for the process of sequencing randomly selected large-insert clones. Genome size, library depth, clone size, and clone distribution are considered relevant properties and perfect overlap detection for contig assembly is assumed. Genome-specific and nonrandom effects are neglected. Order of magnitud...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.gr-1339r
更新日期:2001-02-01 00:00:00
abstract::Evolutionary constraints on gene regulatory elements are poorly understood: Little is known about how the strength of transcription factor binding correlates with DNA sequence conservation, and whether transcription factor binding sites can evolve rapidly while retaining their function. Here we use the model of the NF...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6490707
更新日期:2007-09-01 00:00:00
abstract::We have performed detrended DNA walks on whole prokaryotic genomes, on noncoding sequences and, separately, on each position in codons of coding sequences. Our method enables us to distinguish between the mutational pressure associated with replication and the mutational pressure associated with transcription and othe...
journal_title:Genome research
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Primate pericentromeric regions recently have been shown to exhibit extraordinary evolutionary plasticity. In this paper we report an additional peculiar feature of these regions that we discovered while analyzing, by FISH, the evolutionary conservation of primate phylogenetic chromosome IX. If the position of the cen...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.9.12.1184
更新日期:1999-12-01 00:00:00
abstract::We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequili...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.8.11.1172
更新日期:1998-11-01 00:00:00
abstract::The acquisition of new genes, via horizontal transfer or gene duplication/diversification, has been the dominant mechanism thus far implicated in the evolution of microbial pathogenicity. In contrast, the role of many other modes of evolution--such as changes in gene expression regulation-remains unknown. A transition...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.134080.111
更新日期:2012-10-01 00:00:00
abstract::Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.107920.110
更新日期:2010-10-01 00:00:00
abstract::Orthologous genes that maintain a single-copy status in a broad range of species may indicate a selection against gene duplication. If this is the case, then duplicates of such genes that do survive may have escaped the dosage control by rapid and sizable changes in their function. To test this hypothesis and to devel...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3266405
更新日期:2005-03-01 00:00:00
abstract::The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characteri...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.126573.111
更新日期:2012-02-01 00:00:00
abstract::Identifying transcriptional regulatory elements represents a significant challenge in annotating the genomes of higher vertebrates. We have developed a computational tool, rVista, for high-throughput discovery of cis-regulatory elements that combines clustering of predicted transcription factor binding sites (TFBSs) a...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.225502
更新日期:2002-05-01 00:00:00
abstract::Contamination by present-day human and microbial DNA is one of the major hindrances for large-scale genomic studies using ancient biological material. We describe a new molecular method, U selection, which exploits one of the most distinctive features of ancient DNA--the presence of deoxyuracils--for selective enrichm...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.174201.114
更新日期:2014-09-01 00:00:00
abstract::Through comparative studies of the model organism Arabidopsis thaliana and its close relative Brassica oleracea, we have identified conserved regions that represent potentially functional sequences overlooked by previous Arabidopsis genome annotation methods. A total of 454,274 whole genome shotgun sequences covering ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3176505
更新日期:2005-04-01 00:00:00
abstract::We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program, allowing for assembly of mammalian-size genomes, and also improving the assembly of smaller genomes. Three principal change...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.828403
更新日期:2003-01-01 00:00:00
abstract::Pollen, the male gametophyte of flowering plants, represents an ideal biological system to study developmental processes, such as cell polarity, tip growth, and morphogenesis. Upon hydration, the metabolically quiescent pollen rapidly switches to an active state, exhibiting extremely fast growth. This rapid switch req...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.089060.108
更新日期:2009-10-01 00:00:00
abstract::We compared the genome of the nematode Caenorhabditis elegans to 13% of that of Caenorhabditis briggsae, identifying 252 conserved segments along their chromosomes. We detected 517 chromosomal rearrangements, with the ratio of translocations to inversions to transpositions being approximately 1:1:2. We estimate that t...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.172702
更新日期:2002-06-01 00:00:00
abstract::Few methods are available for mapping the local structure of DNA throughout a genome. The hydroxyl radical cleavage pattern is a measure of the local variation in solvent-accessible surface area of duplex DNA, and thus provides information on the local shape and structure of DNA. We report the construction of a relati...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6073107
更新日期:2007-06-01 00:00:00
abstract::Large scale gene perturbation experiments generate information about the number of genes whose activity is directly or indirectly affected by a gene perturbation. From this information, one can numerically estimate coarse structural network features such as the total number of direct regulatory interactions and the nu...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.193902
更新日期:2002-02-01 00:00:00
abstract::Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. We presen...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.2889405
更新日期:2005-01-01 00:00:00
abstract::PipMaker (http://bio.cse.psu.edu) is a World-Wide Web site for comparing two long DNA sequences to identify conserved segments and for producing informative, high-resolution displays of the resulting alignments. One display is a percent identity plot (pip), which shows both the position in one sequence and the degree ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.10.4.577
更新日期:2000-04-01 00:00:00
abstract::The newly sequenced genome of Monodelphis domestica not only provides the out-group necessary to better understand our own eutherian lineage, but it enables insights into the innovative biology of metatherians. Here, we compare Monodelphis with Homo sequences from alignments of single nucleotides, genes, and whole chr...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6093907
更新日期:2007-07-01 00:00:00