Detection and quantification of mutations in the plasma of patients with colorectal tumors
Detection and quantification of mutations in the plasma of patients with colorectal tumors
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DOI：
10.1073/pnas.0507904102
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发表时间：
2005-11-08
影响因子：
11.1
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
--
作者：
Diehl, F;Li, M;Vogelstein, B
通过分析循环DNA早期发现癌症可能对发病率和死亡率产生重大影响。为了实现这一目标，必须确定癌症患者循环中存在的突变分子的数量，并开发足够灵敏的方法来检测这些突变。使用最近开发的用于此目的的检测方法的修改版本，我们发现晚期结直肠癌患者的血浆中始终含有突变的腺瘤性结肠息肉病（APC）DNA分子。这些患者血浆中APC DNA片段的中位数为47，800/ml，其中8%为突变型。突变型APC分子也在> 60%的患者中检测到：患有早期、可能可治愈的结直肠癌，其水平范围为总APC分子的0.01%至1.7%。这些结果对肿瘤DNA释放到循环中的机制以及基于该现象的诊断测试具有影响。
The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (APC) DNA molecules in their plasma. The median number of APC DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant APC molecules were also detected in > 60% of patients :with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.