Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Fornaro, Lorenzo; Faviana, Pinuccia; De Gregorio, Veronica; Vivaldi, Caterina; Paolicchi, Elisa; Masi, Gianluca; Loupakis, Fotios; Sensi, Elisa; Lupi, Cristiana; Fontanini, Gabriella; Wang, Yuzhuo; Danesi, Romano; Falcone, Alfredo; Crea, Francesco
• Is Part Of: BMC cancer. Volume 15:Issue 1(2015)
• Page Start: 1
• Page End: 6
• Publication Date: 2015-12
• Subjects: BRAF -- Colorectal cancer -- EZH2 -- KRAS -- Polycomb -- Single nucleotide polymorphism; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-015-1889-2
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background The 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 theEZH2 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. Methods 119 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 betweenEZH2 rs3757441 genotypes and EZH2/H3K27me3 expression. Potential associations between EZH2/H3K27me3 expression and clinico-pathological features orKRAS exon 2 andBRAF exon 15 mutations were secondary endpoints. Statistical analysis was performed by chi-square test, T-test or ANOVA. Results The C/C genotype was significantly associated with higher EZH2 (100vs. 44 %;P = 0.019) and H3K27me3 (100vs. 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 andBRAF mutations were not associated with EZH2 or H3K27me3 expression. Conclusion EZH2 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 toKRAS andBRAF testing.