Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression

BMC Cancer

Research Article

Jean-Louis Kemeny¹  Gaelle Judes²  Lucas Dubois²  Yves-Jean Bignon²  Marine Daures²  Dominique Bernard-Gallon²  Marjolaine Ngollo²  Khaldoun Rifai²  Frederique Penault-Llorca³  Laurent Guy⁴  Andre Lebert⁵ 

[1] Department of Biopathology, Gabriel Montpied Hospital, 58 rue Montalembert, 63000, Clermont-Ferrand, France;Department of Oncogenetics, Centre Jean Perrin – CBRV, 28 place Henri Dunant, BP 38, 63001, Clermont-Ferrand, France;INSERM U 1240, IMOST, 58 rue Montalembert-BP184, 63005, Clermont-Ferrand, France;INSERM U 1240, IMOST, 58 rue Montalembert-BP184, 63005, Clermont-Ferrand, France;Department of Biopathology, Centre Jean Perrin, 58 rue Montalembert, 63000, Clermont-Ferrand, France;INSERM U 1240, IMOST, 58 rue Montalembert-BP184, 63005, Clermont-Ferrand, France;Department of Urology, Gabriel Montpied Hospital, 58 rue Montalembert, 63000, Clermont-Ferrand, France;University Blaise Pascal, Institut Pascal UMR 6602 CNRS/UBP, 24 Avenue des Landais, Aubière, France;

关键词: ChIP-on-chip;    Epigenetics;    Histone methylation;    H3K27me3;    Prostate;    Cancer;   

DOI  :  10.1186/s12885-017-3256-y

 received in 2016-09-20, accepted in 2017-04-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundH3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression.MethodsWe investigated genome-wide H3K27me3 histone methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K promoter microarrays to identify differentially-enriched regions in biopsy samples from prostate cancer patients. H3K27me3 marks were assessed in 34 prostate tumors: 11 with Gleason score > 7 (GS > 7), 10 with Gleason score ≤ 7 (GS ≤ 7), and 13 morphologically normal prostate samples.ResultsHere, H3K27me3 profiling identified an average of 386 enriched-genes on promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. We then ran a factorial discriminant analysis (FDA) and compared the enriched genes in prostate-tumor biopsies and normal biopsies using ANOVA to identify significantly differentially-enriched genes. The analysis identified ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes. These genes are possibly associated with prostate cancer. Notably, the H3K27me3 histone mark emerged as a novel regulatory mechanism in poor-prognosis prostate cancer.ConclusionsOur findings point to epigenetic mark H3K27me3 as an important event in prostate carcinogenesis and progression. The results reported here provide new molecular insights into the pathogenesis of prostate cancer.

【 授权许可】

CC BY   
© The Author(s). 2017