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- Title
Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer.
- Authors
Fornaro, Lorenzo; Faviana, Pinuccia; De Gregorio, Veronica; Vivaldi, Caterina; Paolicchi, Elisa; Masi, Gianluca; Loupakis, Fotios; Sensi, Elisa; Lupi, Cristiana; Fontanini, Gabriella; Yuzhuo Wang; Danesi, Romano; Falcone, Alfredo; Crea, Francesco; Wang, Yuzhuo
- Abstract
<bold>Background: </bold>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 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. <bold>Methods: </bold>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 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. <bold>Results: </bold>The 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. <bold>Conclusion: </bold>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 to KRAS and BRAF testing.
- Subjects
SINGLE nucleotide polymorphisms; COLON cancer; POLYCOMB group proteins; BRAF genes; METASTASIS; IMMUNOHISTOCHEMISTRY; STATISTICAL correlation; BIOMARKERS; COLON tumors; GENES; GENETIC polymorphisms; GENETIC mutation; PROGNOSIS; PROTEINS; RECTUM tumors; TRANSFERASES; TUMOR classification; GENOTYPES
- Publication
BMC Cancer, 2015, Vol 15, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-015-1889-2