Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma.
Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10(-9) ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR<10(-3) ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection.
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.
Wei
W
Dai
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.
Arthur Kwok Leung
AK
Cheung
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.
Josephine Mun Yee
JM
Ko
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.
Yue
Y
Cheng
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.
Hong
H
Zheng
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), China.|Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong (SAR), China.
Roger Kai Cheong
RK
Ngan
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), China.|Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), China.
Wai Tong
WT
Ng
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), China.|Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Anne Wing Mui
AW
Lee
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), China.|Department of Oncology, Princess Margaret Hospital, Hong Kong (SAR), China.
Chun Chung
CC
Yau
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.
Victor Ho Fu
VH
Lee
Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), China.|Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), China.
Maria Li
ML
Lung
D002277:Carcinoma; D002896:Chromosomes, Human, Pair 6; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D015201:Meta-Analysis as Topic; D008745:Methylation; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D059467:Transcriptome
D006657:Histones
Chromosome 6p; EBV; Illumina HumanMethylation450; methylome; nasopharyngeal carcinoma