エピジェネティクスと頭頸部がん

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タイトル別名
  • Epigenetics and Head and Neck Cancer
  • エピジェネティクス ト アタマ ケイブ ガン

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<p>Not only genetic changes, such as tumor suppressor gene mutation, proto-oncogene activation and genomic instability, but also epigenetic modifications play fundamental roles in cancer development. The most common examples of epigenetic modifications include DNA methylation, histone modification, small non-coding RNAs, and others.</p><p>Our studies have identified several G protein-coupled receptors (GPCRs) as prognostic factors for head and neck squamous cell carcinoma (HNSCC). Significant epigenetic silencing of GPCR expression by DNA methylation, including that of Galanin (25%), GALR1 (38%), GALR2 (33%), TAC1 (49%), TACR1 (34%), SST (81%) and SSTR1 (64%), has been found in HNSCC than in normal tissue, which is also known to be significantly correlated with the clinical behavior. The group with hypermethylation (more than 4 out of 7 genes) showed a significantly higher percentage of cases with advanced disease, reduced disease-free survival, and a higher recurrence rate.</p><p>We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (54%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. The disease-free survival was lower in patients with 6-11 methylated genes than in those with 0-5 methylated genes. In a multivariate Cox proportional hazards analysis, methylation of E-cadherin, COL1A2, TAC1 and GALR1 was associated with a poor survival. In a joint analysis of these four genes, early-stage HNSCC patients with 2-4 methylated genes had a significantly lower survival rate than those with 0-1 methylated genes.</p><p>Epigenetic modifications can be reversible and therefore be targeted therapeutically by the enzymes involved in DNA methylation and histone modifications. Further study of epigenetic alterations in HNSCC may pave the way for the development of new treatments and/or for elucidation of the carcinogenetic pathway.</p>

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