Widely dispersed p53 mutation in respiratory epithelium - A novel mechanism for field carcinogenesis
Widely dispersed p53 mutation in respiratory epithelium - A novel mechanism for field carcinogenesis
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DOI：
10.1172/jci119748
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发表时间：
1997-10-15
影响因子：
15.9
通讯作者：
Miller, YE
中科院分区：
文献类型：
--
作者：
Franklin, WA;Gazdar, AF;Miller, YE
患有一种呼吸消化道恶性肿瘤的个体发生第二种原发性呼吸消化道肿瘤的几率很高。这种场效应的机制尚未确定。我们研究了一个呼吸道上皮广泛发育异常但无明显癌的个体。尸检时获得的整个气管支气管树包埋在石蜡中，并通过显微切割分离支气管上皮细胞，从显微切割的细胞中提取DNA进行p53肿瘤抑制基因的点突变分析。一个单一的，相同的点突变组成的G：C到T：A的密码子245颠换被确定在支气管上皮细胞从7的10个网站在两个肺。在含有p53突变的部位的上皮细胞形态异常，表现为鳞状化生和轻度至中度增生。在气管支气管树或任何其他部位均未发现浸润性肿瘤，外周血、肾、肝和淋巴结细胞均未显示p53基因异常，吸烟者支气管中普遍存在单个体细胞p53点突变，这表明单个祖细胞支气管上皮克隆可能扩展到支气管粘膜的广泛区域，一种新的机制，现场致癌的呼吸道上皮细胞，可能是重要的，在评估个人的风险，第二原发性肿瘤，以及在制定有效的战略，化学预防肺癌。
Individuals with one aerodigestive tract malignancy have a high incidence of second primary aerodigestive tumors. The mechanism for this field effect has not been determined. We studied an individual with widespread dysplastic changes in the respiratory epithelium but no overt carcinoma, The entire tracheobronchial tree obtained at autopsy was embedded in paraffin, and bronchial epithelial cells were isolated by microdissection, DNA extracted from the microdissected cells was analyzed for point mutations in the p53 tumor suppressor gene. A single, identical point mutation consisting of a G:C to T:A transversion in codon 245 was identified in bronchial epithelium from 7 of 10 sites in both lungs. Epithelium at sites containing the p53 mutation was morphologically abnormal, exhibiting squamous metaplasia and mild to moderate atypia. No invasive tumor was found in the tracheobronchial tree or any other location, Cells from peripheral blood, kidney, liver, and lymph node exhibited no abnormality in the p53 gene, The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker suggests that a single progenitor bronchial epithelial clone may expand to populate broad areas of the bronchial mucosa-a novel mechanism for field carcinogenesis in the respiratory epithelium that may be of importance in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cancer.