A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes
| Autor: | Gangotri Siddappa, Jayalakshmi Nair, Neeraja M. Krishnan, Amritha Suresh, Vinayak Palve, Moni Abraham Kuriakose, Vikram Kekatpure, Kunal Dhas, Jamir Bagwan, Binay Panda |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Down-Regulation Gene Expression Biology Metastasis 03 medical and health sciences Tongue Gene expression medicine Humans Promoter Regions Genetic Molecular Biology Gene Neoplasm Staging Squamous Cell Carcinoma of Head and Neck Methylation DNA Methylation medicine.disease Tongue Neoplasms RPS6KA2 030104 developmental biology Differentially methylated regions medicine.anatomical_structure Oncology Head and Neck Neoplasms DNA methylation Carcinoma Squamous Cell Cancer research Genome-Wide Association Study |
| Zdroj: | Molecular Cancer Research. 14:805-819 |
| ISSN: | 1557-3125 1541-7786 |
| Popis: | Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of aggressive tumors in the head and neck region that spread early to lymph nodes and have a higher incidence of regional failure. In addition, there is a rising incidence of oral tongue cancer in younger populations. Studies on functional DNA methylation changes linked with altered gene expression are critical for understanding the mechanisms underlying tumor development and metastasis. Such studies also provide important insight into biomarkers linked with viral infection, tumor metastasis, and patient survival in OTSCC. Therefore, we performed genome-wide methylation analysis of tumors (N = 52) and correlated altered methylation with differential gene expression. The minimal tumor-specific DNA 5-methylcytosine signature identified genes near 16 different differentially methylated regions, which were validated using genomic data from The Cancer Genome Atlas cohort. In our cohort, hypermethylation of MIR10B was significantly associated with the differential expression of its target genes NR4A3 and BCL2L11 (P = 0.0125 and P = 0.014, respectively), which was inversely correlated with disease-free survival (P = 9E−15 and P = 2E−15, respectively) in patients. Finally, differential methylation in FUT3, TRIM5, TSPAN7, MAP3K8, RPS6KA2, SLC9A9, and NPAS3 genes was found to be predictive of certain clinical and epidemiologic parameters. Implications: This study reveals a functional minimal methylation profile in oral tongue tumors with associated risk habits, clinical, and epidemiologic outcomes. In addition, NR4A3 downregulation and correlation with patient survival suggests a potential target for therapeutic intervention in oral tongue tumors. Data from the current study are deposited in the NCBI Geo database (accession number GSE75540). Mol Cancer Res; 14(9); 805–19. ©2016 AACR. |
| Databáze: | OpenAIRE |
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