WFRF:(Valli G.)
Search: WFRF:(Valli G.) > (2020-2023) > A G316A Polymorphis...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03483naa a2200673 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:146443592 | |
| 003 | SwePub | |
| 008 | 240701s2021 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1464435922 URI |
| 024 | 7 | a https://doi.org/10.3390/cancers130818072 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Gamble, LD4 aut |
| 245 | 1 0 | a A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma |
| 264 | c 2021-04-09 | |
| 264 | 1 | b MDPI AG,c 2021 |
| 520 | a Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein. | |
| 700 | 1 | a Purgato, S4 aut |
| 700 | 1 | a Henderson, MJ4 aut |
| 700 | 1 | a Di Giacomo, S4 aut |
| 700 | 1 | a Russell, AJ4 aut |
| 700 | 1 | a Pigini, P4 aut |
| 700 | 1 | a Murray, J4 aut |
| 700 | 1 | a Valli, E4 aut |
| 700 | 1 | a Milazzo, G4 aut |
| 700 | 1 | a Giorgi, FM4 aut |
| 700 | 1 | a Cowley, M4 aut |
| 700 | 1 | a Ashton, LJ4 aut |
| 700 | 1 | a Bhalshankar, J4 aut |
| 700 | 1 | a Schleiermacher, G4 aut |
| 700 | 1 | a Rihani, Au Karolinska Institutet4 aut |
| 700 | 1 | a Van Maerken, T4 aut |
| 700 | 1 | a Vandesompele, J4 aut |
| 700 | 1 | a Speleman, F4 aut |
| 700 | 1 | a Versteeg, R4 aut |
| 700 | 1 | a Koster, J4 aut |
| 700 | 1 | a Eggert, A4 aut |
| 700 | 1 | a Noguera, R4 aut |
| 700 | 1 | a Stallings, RL4 aut |
| 700 | 1 | a Tonini, GP4 aut |
| 700 | 1 | a Fong, K4 aut |
| 700 | 1 | a Vaksman, Z4 aut |
| 700 | 1 | a Diskin, SJ4 aut |
| 700 | 1 | a Maris, JM4 aut |
| 700 | 1 | a London, WB4 aut |
| 700 | 1 | a Marshall, GM4 aut |
| 700 | 1 | a Ziegler, DS4 aut |
| 700 | 1 | a Hogarty, MD4 aut |
| 700 | 1 | a Perini, G4 aut |
| 700 | 1 | a Norris, MD4 aut |
| 700 | 1 | a Haber, M4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Cancersd : MDPI AGg 13:8q 13:8x 2072-6694 |
| 856 | 4 | u https://www.mdpi.com/2072-6694/13/8/1807/pdf |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:146443592 |
| 856 | 4 8 | u https://doi.org/10.3390/cancers13081807 |
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- Purgato, S
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- Murray, J
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- Milazzo, G
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- Van Maerken, T
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- Diskin, SJ
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