The epigenetic landscape of oral squamous cell carcinoma

被引：71
作者：
Jithesh, P. V. [1 ]
Risk, J. M. [1 ,2 ]
Schache, A. G. [1 ,3 ]
Dhanda, J. [1 ]
Lane, B. [4 ]
Liloglou, T. [1 ]
Shaw, R. J. [1 ,3 ]
机构：
[1] Univ Liverpool, Liverpool Canc Res UK Ctr, Dept Mol & Clin Canc Med, Inst Translat Med, Liverpool L69 3GL, Merseyside, England
[2] Univ Liverpool, Sch Dent, Liverpool L69 3GL, Merseyside, England
[3] Aintree Univ Hosp NHS Fdn Trust, Reg Maxillofacial Unit, Liverpool, Merseyside, England
[4] Liverpool NIHR Pancreas Biomed Res Unit, Liverpool, Merseyside, England
来源：
BRITISH JOURNAL OF CANCER | 2013年 / 108卷 / 02期
关键词：
oral squamous cell carcinoma; DNA methylation; microarray; prognosis; ISLAND METHYLATOR PHENOTYPE; INDEPENDENT PROGNOSTIC-FACTOR; DNA METHYLATION; PROMOTER HYPERMETHYLATION; HUMAN BREAST; GLOBAL HYPOMETHYLATION; NECK-CANCER; HEAD; GENE; EXPRESSION;
D O I：
10.1038/bjc.2012.568
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs. Methods: DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival. Results: Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series. Conclusion: Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.
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页码：370 / 379
页数：10
相关论文
共 62 条
[11]  
Davis S., 2012, Methylumi: Handle illumina methylation data
[12]   Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis [J].
Du, Pan ;
Zhang, Xiao ;
Huang, Chiang-Ching ;
Jafari, Nadereh ;
Kibbe, Warren A. ;
Hou, Lifang ;
Lin, Simon M. .
BMC BIOINFORMATICS, 2010, 11
[13]   Gene expression profiles of head and neck carcinomas from Sudanese and Norwegian patients reveal common biological pathways regardless of race and lifestyle [J].
Dysvik, B ;
Vasstrand, EN ;
Lovlie, R ;
Elgindi, OAA ;
Kross, KW ;
Aarstad, HJ ;
Johannessen, AC ;
Jonassen, I ;
Ibrahim, SO .
CLINICAL CANCER RESEARCH, 2006, 12 (04) :1109-1120
[14]   Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers [J].
Etoh, T ;
Kanai, Y ;
Ushijima, S ;
Nakagawa, T ;
Nakanishi, Y ;
Sasako, M ;
Kitano, S ;
Hirohashi, S .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (02) :689-699
[15]   NID2 and HOXA9 Promoter Hypermethylation as Biomarkers for Prevention and Early Detection in Oral Cavity Squamous Cell Carcinoma Tissues and Saliva [J].
Guerrero-Preston, R. ;
Soudry, E. ;
Acero, J. ;
Orera, M. ;
Moreno-Lopez, L. ;
Macia-Colon, G. ;
Jaffe, A. ;
Berdasco, M. ;
Ili-Gangas, C. ;
Brebi-Mieville, P. ;
Fu, Y. ;
Engstrom, C. ;
Irizarry, R. A. ;
Esteller, M. ;
Westra, W. ;
Koch, W. ;
Califano, J. ;
Sidransky, D. .
CANCER PREVENTION RESEARCH, 2011, 4 (07) :1061-1072
[16]   Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma [J].
Ha, PK ;
Califano, JA .
LANCET ONCOLOGY, 2006, 7 (01) :77-82
[17]   Promoter Methylation in Head and Neck Squamous Cell Carcinoma Cell Lines Is Significantly Different than Methylation in Primary Tumors and Xenografts [J].
Hennessey, Patrick T. ;
Ochs, Michael F. ;
Mydlarz, Wojciech W. ;
Hsueh, Wayne ;
Cope, Leslie ;
Yu, Wayne ;
Califano, Joseph A. .
PLOS ONE, 2011, 6 (05)
[18]   Copy number variation has little impact on bead-array-based measures of DNA methylation [J].
Houseman, E. Andres ;
Christensen, Brock C. ;
Karagas, Margaret R. ;
Wrensch, Margaret R. ;
Nelson, Heather H. ;
Wiemels, Joseph L. ;
Zheng, Shichun ;
Wiencke, John K. ;
Kelsey, Karl T. ;
Marsit, Carmen J. .
BIOINFORMATICS, 2009, 25 (16) :1999-2005
[19]   Gene expression profile in oral squamous cell carcinomas and matching normal oral mucosal tissues from black Africans and white Caucasians:: the case of the Sudan vs. Norway [J].
Ibrahim, SO ;
Aarsæther, N ;
Holsve, MK ;
Kross, KW ;
Heimdal, JH ;
Aarstad, JH ;
Liavaag, PG ;
Elgindi, OAA ;
Johannessen, AC ;
Lillehaug, JR ;
Vasstrand, EN .
ORAL ONCOLOGY, 2003, 39 (01) :37-48
[20]   Methylation Pattern of Calcitonin (CALCA) Gene in Pediatric Acute Leukemia [J].
Ismail, Eman Abdel Rahman ;
El-Mogy, Mahira Ismail ;
Mohamed, Deena Samir ;
El-Farrash, Rania Ali Hassan .
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2011, 33 (07) :534-542
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