Palmisano W A, Divine K K, Saccomanno G, Gilliland F D, Baylin S B, Herman J G, Belinsky S A
Lovelace Respiratory Research Institute, Lung Cancer Program, Albuquerque, New Mexico 87185, USA.
Cancer Res. 2000 Nov 1;60(21):5954-8.
Despite the promise of using DNA markers for the early detection of cancer, none has proven universally applicable to the most common and lethal forms of human malignancy. Lung carcinoma, the leading cause of tumor-related death, is a key example of a cancer for which mortality could be greatly reduced through the development of sensitive molecular markers detectable at the earliest stages of disease. By increasing the sensitivity of a PCR approach to detect methylated DNA sequences, we now demonstrate that aberrant methylation of the p16 and/or O6-methyl-guanine-DNA methyltransferase promoters can be detected in DNA from sputum in 100% of patients with squamous cell lung carcinoma up to 3 years before clinical diagnosis. Moreover, the prevalence of these markers in sputum from cancer-free, high-risk subjects approximates lifetime risk for lung cancer. The use of aberrant gene methylation as a molecular marker system seems to offer a potentially powerful approach to population-based screening for the detection of lung cancer, and possibly the other common forms of human cancer.
尽管利用DNA标记物进行癌症早期检测前景广阔，但尚无一种标记物被证明能普遍应用于人类最常见且致命的恶性肿瘤形式。肺癌是肿瘤相关死亡的主要原因，是一种若能开发出在疾病最早期阶段就能检测到的敏感分子标记物，死亡率就能大幅降低的癌症典型例子。通过提高检测甲基化DNA序列的PCR方法的灵敏度，我们现在证明，在临床诊断前长达3年的时间里，100%的鳞状细胞肺癌患者痰液DNA中都能检测到p16和/或O6-甲基鸟嘌呤-DNA甲基转移酶启动子的异常甲基化。此外，这些标记物在无癌高危受试者痰液中的流行率接近肺癌的终生风险。将异常基因甲基化用作分子标记系统似乎为基于人群的肺癌检测筛查，以及可能的其他常见人类癌症检测提供了一种潜在的强大方法。
