FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2064503485> ?p ?o ?g. }

• W2064503485 endingPage "3586" @default.
• W2064503485 startingPage "3577" @default.
• W2064503485 abstract "One major challenge in cancer research is to understand the complex interplay between the DNA damage response (DDR), genomic integrity, and tumor development. To address these issues, we analyzed 43 bladder tumor genomes from 22 patients using single nucleotide polymorphism (SNP) arrays, and tissue expression of multiple DDR proteins, including Timeless and its interaction partner Tipin. The SNP profiles confirmed and extended known copy number alterations (CNAs) at high resolution, showed clustering of CNAs at nine common fragile sites, and revealed that most metachronous tumors were clonally related. The occurrence of many novel uniparental disomy regions (UPDs) was of potential functional importance in some tumors because UPDs spanned mutated FGFR3 and PIK3CA alleles, and also homozygous deletion of the CDKN2A tumor suppressor locus. The DDR signaling as evaluated by phospho-epitope-specific antibodies against Ser139-phosphorylated H2A histone family member X (γH2AX), ataxia telangiectasia mutated (ATM), and ATM- and Rad3-related (ATR) was commonly activated in tumors with both moderate and high extent of accumulated genomic aberrations, the latter tumors showing a more frequent loss of ATM expression. Strikingly, the tumor genomes exhibiting the most complex alterations were associated with a high Ki67-proliferation index, abundant Timeless but not Tipin expression, aberrant p53 expression, and homozygous CDKN2A deletions. Of clinical relevance, evaluation of a tissue microarray (TMA; n=319) showed that abundant Timeless expression was associated with risk of progression to muscle-invasive disease (P<0.0005; hazard ratio, 2.4; 95% confidence interval, 1.6-3.8) and higher T stage (P<0.05). Univariate analysis confirmed this association (P=0.006) in an independent cohort (n=241) but statistical significance was not reached in a multivariate model. Overall, our results are consistent with DDR activation preceding the accumulation of genomic aberrations. Tumors with extensive genomic rearrangements were associated with inactivation of CDKN2A, excessive proliferation, and robust Timeless expression, the latter also correlating with the risk of disease progression. Moreover, we provide evidence to suggest that UPDs likely contribute to bladder tumorigenesis." @default.
• W2064503485 created "2016-06-24" @default.
• W2064503485 creator A5003132091 @default.
• W2064503485 creator A5014448997 @default.
• W2064503485 creator A5014868163 @default.
• W2064503485 creator A5019478811 @default.
• W2064503485 creator A5019738724 @default.
• W2064503485 creator A5019975916 @default.
• W2064503485 creator A5020909384 @default.
• W2064503485 creator A5027336843 @default.
• W2064503485 creator A5029793411 @default.
• W2064503485 creator A5050758135 @default.
• W2064503485 creator A5070573139 @default.
• W2064503485 creator A5083958165 @default.
• W2064503485 creator A5084392281 @default.
• W2064503485 creator A5090729430 @default.
• W2064503485 date "2012-08-27" @default.
• W2064503485 modified "2023-10-18" @default.
• W2064503485 title "A high resolution genomic portrait of bladder cancer: correlation between genomic aberrations and the DNA damage response" @default.
• W2064503485 cites W1538419182 @default.
• W2064503485 cites W1965239527 @default.
• W2064503485 cites W1969270435 @default.
• W2064503485 cites W1972217867 @default.
• W2064503485 cites W1984065010 @default.
• W2064503485 cites W1988992319 @default.
• W2064503485 cites W1990903366 @default.
• W2064503485 cites W1993579360 @default.
• W2064503485 cites W1994492382 @default.
• W2064503485 cites W1996926758 @default.
• W2064503485 cites W2002045993 @default.
• W2064503485 cites W2004287746 @default.
• W2064503485 cites W2008781125 @default.
• W2064503485 cites W2009166249 @default.
• W2064503485 cites W2011595291 @default.
• W2064503485 cites W2013370526 @default.
• W2064503485 cites W2013493332 @default.
• W2064503485 cites W2018561776 @default.
• W2064503485 cites W2021341670 @default.
• W2064503485 cites W2021492361 @default.
• W2064503485 cites W2026848473 @default.
• W2064503485 cites W2029368807 @default.
• W2064503485 cites W2033277972 @default.
• W2064503485 cites W2034636599 @default.
• W2064503485 cites W2041156660 @default.
• W2064503485 cites W2055917646 @default.
• W2064503485 cites W2059971436 @default.
• W2064503485 cites W2061305437 @default.
• W2064503485 cites W2065434335 @default.
• W2064503485 cites W2065779053 @default.
• W2064503485 cites W2071734901 @default.
• W2064503485 cites W2074730941 @default.
• W2064503485 cites W2077436902 @default.
• W2064503485 cites W2081843726 @default.
• W2064503485 cites W2082559623 @default.
• W2064503485 cites W2086333179 @default.
• W2064503485 cites W2090002021 @default.
• W2064503485 cites W2095584158 @default.
• W2064503485 cites W2102922697 @default.
• W2064503485 cites W2104655450 @default.
• W2064503485 cites W2106787323 @default.
• W2064503485 cites W2109948920 @default.
• W2064503485 cites W2114860131 @default.
• W2064503485 cites W2119803525 @default.
• W2064503485 cites W2121135241 @default.
• W2064503485 cites W2127622729 @default.
• W2064503485 cites W2129769331 @default.
• W2064503485 cites W2145200068 @default.
• W2064503485 cites W2160866940 @default.
• W2064503485 cites W2162813066 @default.
• W2064503485 cites W2164585152 @default.
• W2064503485 cites W2170538546 @default.
• W2064503485 cites W2171297405 @default.
• W2064503485 doi "https://doi.org/10.1038/onc.2012.381" @default.
• W2064503485 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22926521" @default.
• W2064503485 hasPublicationYear "2012" @default.
• W2064503485 type Work @default.
• W2064503485 sameAs 2064503485 @default.
• W2064503485 citedByCount "32" @default.
• W2064503485 countsByYear W20645034852012 @default.
• W2064503485 countsByYear W20645034852013 @default.
• W2064503485 countsByYear W20645034852014 @default.
• W2064503485 countsByYear W20645034852015 @default.
• W2064503485 countsByYear W20645034852016 @default.
• W2064503485 countsByYear W20645034852017 @default.
• W2064503485 countsByYear W20645034852018 @default.
• W2064503485 countsByYear W20645034852019 @default.
• W2064503485 countsByYear W20645034852020 @default.
• W2064503485 countsByYear W20645034852021 @default.
• W2064503485 countsByYear W20645034852022 @default.
• W2064503485 countsByYear W20645034852023 @default.
• W2064503485 crossrefType "journal-article" @default.
• W2064503485 hasAuthorship W2064503485A5003132091 @default.
• W2064503485 hasAuthorship W2064503485A5014448997 @default.
• W2064503485 hasAuthorship W2064503485A5014868163 @default.
• W2064503485 hasAuthorship W2064503485A5019478811 @default.
• W2064503485 hasAuthorship W2064503485A5019738724 @default.
• W2064503485 hasAuthorship W2064503485A5019975916 @default.
• W2064503485 hasAuthorship W2064503485A5020909384 @default.

• next