BMC Cancer | |
Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer | |
Research Article | |
Elisa Paolicchi1  Francesco Crea2  Yuzhuo Wang3  Romano Danesi4  Alfredo Falcone5  Lorenzo Fornaro5  Gianluca Masi5  Caterina Vivaldi5  Veronica De Gregorio5  Fotios Loupakis5  Elisa Sensi6  Cristiana Lupi6  Gabriella Fontanini6  Pinuccia Faviana6  | |
[1] Department of Biology, Unit of Genetics, University of Pisa, Pisa, Italy;Experimental Therapeutics, BCCA Cancer Research Centre, Vancouver, BC, Canada;Department of Life Health and Chemical Sciences, The Open Universit, Milton Keynes, UK;Experimental Therapeutics, BCCA Cancer Research Centre, Vancouver, BC, Canada;Vancouver Prostate Centre, Vancouver, BC, Canada;Pharmacology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy;Unit of Pathology, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy; | |
关键词: BRAF; Colorectal cancer; EZH2; KRAS; Polycomb; Single nucleotide polymorphism; | |
DOI : 10.1186/s12885-015-1889-2 | |
received in 2015-06-15, accepted in 2015-10-30, 发布年份 2015 | |
来源: Springer | |
【 摘 要 】
BackgroundThe enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking.Methods119 primary CRCs were analyzed. SNP was evaluated by real-time PCR from colonic healthy tissue, while EZH2 and H3K27me3 expression were studied by immunohistochemistry. We primarily looked for correlation between EZH2 rs3757441 genotypes and EZH2/H3K27me3 expression. Potential associations between EZH2/H3K27me3 expression and clinico-pathological features or KRAS exon 2 and BRAF exon 15 mutations were secondary endpoints. Statistical analysis was performed by chi-square test, T-test or ANOVA.ResultsThe C/C genotype was significantly associated with higher EZH2 (100 vs. 44 %; P = 0.019) and H3K27me3 (100 vs. 38 %; P = 0.009) staining intensity compared with C/T and T/T. EZH2 3+ staining significantly correlated with stronger H3K27me3 expression (P = 0.039). KRAS and BRAF mutations were not associated with EZH2 or H3K27me3 expression.ConclusionEZH2 rs3757441 C/C genotype is associated with stronger EZH2 and H3K27me3 immunoreactivity in primary CRC: this SNP may serve as a promising biomarker for EZH2-targeting agents and may add independent information to KRAS and BRAF testing.
【 授权许可】
CC BY
© Fornaro et al. 2015
【 预 览 】
Files | Size | Format | View |
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RO202311104479174ZK.pdf | 1114KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]