DNA methylation profiling reveals novel diagnostic biomarkers in renal cell carcinoma.
DNA methylation profiling reveals novel diagnostic biomarkers in renal cell carcinoma.
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DOI：
10.1186/s12916-014-0235-x
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发表时间：
2014-12-04
期刊：
影响因子：
9.3
通讯作者：
Myers RM
中科院分区：
文献类型：
--
作者：
Lasseigne BN;Burwell TC;Patil MA;Absher DM;Brooks JD;Myers RM
肾细胞癌（RCC）是美国第十大最常诊断的癌症。虽然转移时通常是致命的，但当肿瘤局限于肾脏且肿瘤体积小时，RCC可以通过手术成功治疗。由于大多数早期肾肿瘤不会产生症状，因此迫切需要生物标志物来检测癌症的存在，并在治疗期间和治疗后监测患者。我们研究了来自96名患者的不同组织学肾细胞癌和良性邻近肾组织的全基因组DNA甲基化改变。我们观察到肿瘤和良性邻近组织之间普遍存在甲基化差异，特别是在免疫、g蛋白偶联受体和代谢相关基因中。此外，我们确定了一组DNA甲基化生物标志物，可以可靠地将所有最常见的肾癌组织学亚型中的肿瘤与良性邻近组织区分开来，第二组DNA甲基化生物标志物也可以专门用于透明细胞肾细胞癌肿瘤。这组生物标志物在Cancer Genome Atlas透明细胞、乳头状和憎色肾细胞癌数据集中的1000多个组织中独立验证，具有优异的性能特征。这些DNA甲基化谱提供了对肾细胞癌病因学的深入了解，最重要的是，证明了用于肾癌早期检测的临床适用的生物标志物。本文的在线版本（doi:10.1186/s12916-014-0235-x）包含补充材料，可供授权用户使用。
Renal cell carcinoma (RCC) is the tenth most commonly diagnosed cancer in the United States. While it is usually lethal when metastatic, RCC is successfully treated with surgery when tumors are confined to the kidney and have low tumor volume. Because most early stage renal tumors do not result in symptoms, there is a strong need for biomarkers that can be used to detect the presence of the cancer as well as to monitor patients during and after therapy. We examined genome-wide DNA methylation alterations in renal cell carcinomas of diverse histologies and benign adjacent kidney tissues from 96 patients. We observed widespread methylation differences between tumors and benign adjacent tissues, particularly in immune-, G-protein coupled receptor-, and metabolism-related genes. Additionally, we identified a single panel of DNA methylation biomarkers that reliably distinguishes tumor from benign adjacent tissue in all of the most common kidney cancer histologic subtypes, and a second panel does the same specifically for clear cell renal cell carcinoma tumors. This set of biomarkers were validated independently with excellent performance characteristics in more than 1,000 tissues in The Cancer Genome Atlas clear cell, papillary, and chromophobe renal cell carcinoma datasets. These DNA methylation profiles provide insights into the etiology of renal cell carcinoma and, most importantly, demonstrate clinically applicable biomarkers for use in early detection of kidney cancer. The online version of this article (doi:10.1186/s12916-014-0235-x) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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期刊：
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影响因子：
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