DNA hypermethylation in papillary renal cell carcinoma.

作者: Jörg Ellinger , Daniel Holl , Philipp Nuhn , Philip Kahl , Nicolas Haseke

DOI: 10.1111/J.1464-410X.2010.09468.X

关键词: Histone methylationCarcinogenesisDNA methylationCarcinomaKidney cancerCystectomyMedicinePapillary urothelial neoplasm of low malignant potentialPathologyBladder cancer

摘要: What’s known on the subject? and What does study add? Epigenetic alterations play an essential role during carcinogenesis, earlier studies suggested that global histone modification levels are predictive for patients’ outcome in various tumour entities (e.g. prostate, lung, breast kidney cancer). So far, only smaller H3K9 acetylation patients with papillary urothelial neoplasm of low malignant potential (PUNLMP) H2AX phosphorylation non-muscle invasive bladder cancer exist; both indicate prognostic relevance cancer. We demonstrate methylation (H3K4, H4K20) decrease from normal tissue over muscle to metastases. Histone modifications correlated advanced pathological stage cancer. Furthermore, H4K20me3 appeared be specific survival muscle-invasive undergoing radical cystectomy. OBJECTIVE To investigate pattern DNA CpG island hypermethylation renal cell carcinoma (pRCC). MATERIAL AND METHODS DNA pRCC (n= 32) adjacent 15) was isolated. A quantitative methylation-specific PCR performed analyse at APC (actin beta), CDH1 (E-cadherin), GSTP1 (glutathione S-transferase pi 1), RASSF1A (Ras association domain family member 1A) TIMP3 (TIMP metallopeptidase inhibitor 3); a sequence ACTB without used normalize input calculate relative amount methylated (normalized index methylation, NIM). RESULTS RASSF1A observed most samples (100 vs 94.4%), but median NIM significantly higher (2.11 0.61; P < 0.001). allowed discrimination sensitivity 87.5% specificity 73.3% as determined via receiver operator characteristic analysis (area under curve = 0.814). Hypermethylation (3.0 6.7%), (15.6 0%), (21.9 6.7%) (6.3 0%) infrequent tissue. (P= 0.015), showed trend towards shorter recurrence-free (log-rank P= 0.057). The number gene sites 0.007) lymph node metastasis 0.008). CONCLUSIONS DNA is common irrespective histological subtype, also frequently seen lower Aberrant could marker pRCC.

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