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  • 1
    German Medical Science GMS Publishing House; Düsseldorf
    In:  133. Kongress der Deutschen Gesellschaft für Chirurgie; 20160426-20160429; Berlin; DOC16dgch392 /20160421/
    Publication Date: 2016-04-22
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Abstract: Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of 〉 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.
    Type of Publication: Journal article published
    PubMed ID: 23410972
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  • 3
    Abstract: 6q12-22 is the second most commonly deleted genomic region in prostate cancer. Mapping studies have described a minimally deleted area at 6q15, containing MAP3K7/TAK1, which was recently shown to have tumor suppressive properties. To determine prevalence and clinical significance of MAP3K7 alterations in prostate cancer, a tissue microarray containing 4699 prostate cancer samples was analyzed by fluorescence in situ hybridization. Heterozygous MAP3K7 deletions were found in 18.48% of 2289 interpretable prostate cancers. MAP3K7 deletions were significantly associated with advanced tumor stage (P〈0.0001), high Gleason grade (P〈0.0001), lymph node metastasis (P〈0.0108) and early biochemical recurrence (P〈0.0001). MAP3K7 alterations were typically limited to the loss of one allele as homozygous deletions were virtually absent and sequencing analyses revealed no evidence for MAP3K7 mutations in 15 deleted and in 14 non-deleted cancers. There was a striking inverse association of MAP3K7 deletions and TMPRSS2:ERG fusion status with 26.7% 6q deletions in 1125 ERG-negative and 11.1% 6q deletions in 1198 ERG-positive cancers (P〈0.0001). However, the strong prognostic role of 6q deletions was retained in both ERG-positive and ERG-negative cancers (P〈0.0001 each). In summary, our study identifies MAP3K7 deletion as a prominent feature in ERG-negative prostate cancer with strong association to tumor aggressiveness. MAP3K7 alterations are typically limited to one allele of the gene. Together with the demonstrated tumor suppressive function in cell line experiments and lacking evidence for inactivation through hypermethylation, these results indicate MAP3K7 as a gene for which haploinsufficency is substantially tumorigenic.
    Type of Publication: Journal article published
    PubMed ID: 23370768
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  • 4
    Abstract: Prostate cancer is driven by a combination of genetic and/or epigenetic alterations. Epigenetic alterations are frequently observed in all human cancers, yet how aberrant epigenetic signatures are established is poorly understood. Here we show that the gene encoding BAZ2A (TIP5), a factor previously implicated in epigenetic rRNA gene silencing, is overexpressed in prostate cancer and is paradoxically involved in maintaining prostate cancer cell growth, a feature specific to cancer cells. BAZ2A regulates numerous protein-coding genes and directly interacts with EZH2 to maintain epigenetic silencing at genes repressed in metastasis. BAZ2A overexpression is tightly associated with a molecular subtype displaying a CpG island methylator phenotype (CIMP). Finally, high BAZ2A levels serve as an independent predictor of biochemical recurrence in a cohort of 7,682 individuals with prostate cancer. This work identifies a new aberrant role for the epigenetic regulator BAZ2A, which can also serve as a useful marker for metastatic potential in prostate cancer
    Type of Publication: Journal article published
    PubMed ID: 25485837
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  • 5
    Publication Date: 2012-12-22
    Description: Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paterson, Andrew H -- Wendel, Jonathan F -- Gundlach, Heidrun -- Guo, Hui -- Jenkins, Jerry -- Jin, Dianchuan -- Llewellyn, Danny -- Showmaker, Kurtis C -- Shu, Shengqiang -- Udall, Joshua -- Yoo, Mi-jeong -- Byers, Robert -- Chen, Wei -- Doron-Faigenboim, Adi -- Duke, Mary V -- Gong, Lei -- Grimwood, Jane -- Grover, Corrinne -- Grupp, Kara -- Hu, Guanjing -- Lee, Tae-ho -- Li, Jingping -- Lin, Lifeng -- Liu, Tao -- Marler, Barry S -- Page, Justin T -- Roberts, Alison W -- Romanel, Elisson -- Sanders, William S -- Szadkowski, Emmanuel -- Tan, Xu -- Tang, Haibao -- Xu, Chunming -- Wang, Jinpeng -- Wang, Zining -- Zhang, Dong -- Zhang, Lan -- Ashrafi, Hamid -- Bedon, Frank -- Bowers, John E -- Brubaker, Curt L -- Chee, Peng W -- Das, Sayan -- Gingle, Alan R -- Haigler, Candace H -- Harker, David -- Hoffmann, Lucia V -- Hovav, Ran -- Jones, Donald C -- Lemke, Cornelia -- Mansoor, Shahid -- ur Rahman, Mehboob -- Rainville, Lisa N -- Rambani, Aditi -- Reddy, Umesh K -- Rong, Jun-kang -- Saranga, Yehoshua -- Scheffler, Brian E -- Scheffler, Jodi A -- Stelly, David M -- Triplett, Barbara A -- Van Deynze, Allen -- Vaslin, Maite F S -- Waghmare, Vijay N -- Walford, Sally A -- Wright, Robert J -- Zaki, Essam A -- Zhang, Tianzhen -- Dennis, Elizabeth S -- Mayer, Klaus F X -- Peterson, Daniel G -- Rokhsar, Daniel S -- Wang, Xiyin -- Schmutz, Jeremy -- England -- Nature. 2012 Dec 20;492(7429):423-7. doi: 10.1038/nature11798.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Genome Mapping Laboratory, University of Georgia, Athens, Georgia 30602, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; *Biological Evolution ; Cacao/genetics ; Chromosomes, Plant/genetics ; *Cotton Fiber ; Diploidy ; Gene Duplication/genetics ; Genes, Plant/genetics ; Genome, Plant/*genetics ; Gossypium/classification/*genetics ; Molecular Sequence Annotation ; Phylogeny ; *Polyploidy ; Vitis/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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