Meltzer S J, Yin J, Huang Y, McDaniel T K, Newkirk C, Iseri O, Vogelstein B, Resau J H
Department of Medicine, University of Maryland, Baltimore.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4976-80. doi: 10.1073/pnas.88.11.4976.
Loss of heterozygosity affecting chromosome 17p has been detected at high frequencies in a variety of human tumors, including cancers of the colon, breast, lung, and brain. One presumed target of these losses is p53, a tumor suppressor gene located on 17p. To our knowledge, loss of heterozygosity has not yet been reported at any locus, including p53, in human esophageal cancer. Moreover, current methods of detecting loss of heterozygosity depend on the availability of large amounts of high molecular weight DNA, making the study of small biopsy specimens or paraffin-embedded tissues problematic. We examined 52 primary human esophageal neoplasms for loss of heterozygosity affecting the p53 gene by using the polymerase chain reaction. Loss of one allele was detected in 52% of informative cases and was more common in squamous carcinomas than in adenocarcinomas. Southern blot analysis was used to confirm polymerase chain reaction-derived data. The identification of allelic loss in approximately half of the tumors analyzed supports the hypothesis that inactivation of p53 is involved in the pathogenesis of esophageal cancer.
在包括结肠癌、乳腺癌、肺癌和脑癌在内的多种人类肿瘤中，已高频检测到影响17号染色体短臂（17p）的杂合性缺失。这些缺失的一个假定靶点是p53，它是位于17p上的一种肿瘤抑制基因。据我们所知，在人类食管癌的任何位点，包括p53位点，尚未报道过杂合性缺失。此外，目前检测杂合性缺失的方法依赖于大量高分子量DNA的可用性，这使得对小活检标本或石蜡包埋组织的研究存在问题。我们使用聚合酶链反应检测了52例原发性人类食管肿瘤中影响p53基因的杂合性缺失。在52%的信息性病例中检测到一个等位基因缺失，且在鳞状细胞癌中比在腺癌中更常见。采用Southern印迹分析来确认聚合酶链反应获得的数据。在所分析的约一半肿瘤中鉴定出等位基因缺失，这支持了p53失活参与食管癌发病机制的假说。
