Boynton R F, Blount P L, Yin J, Brown V L, Huang Y, Tong Y, McDaniel T, Newkirk C, Resau J H, Raskind W H, Haggitt R C, Reid B J, Meltzer S J
Department of Medicine (GI Division), University of Maryland School of Medicine, Baltimore.
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3385-8. doi: 10.1073/pnas.89.8.3385.
The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity of APC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers. They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.
肿瘤抑制基因APC最近被鉴定出来，其cDNA是从5号染色体q21区域克隆得到的。在遗传性综合征家族性腺瘤性息肉病中可发现影响APC的点突变，而在散发性结肠癌中也有关于APC及与之紧密连锁的基因MCC的点突变报道，同时还报道了5号染色体q臂杂合性缺失。据我们所知，除肺癌外，尚未在其他任何人类癌症中描述过涉及APC或MCC或两者的杂合性缺失情况。我们运用聚合酶链反应和DNA含量流式细胞术细胞核分选技术，检测了30例原发性人类食管癌中APC或MCC或两者的杂合性缺失情况。在26例信息充分的病例中，77%检测到一个等位基因缺失。这些数据表明，包括APC和MCC基因位点在内的5号染色体q臂区域的杂合性缺失与大多数人类食管癌的发生和/或进展有关。这意味着5号染色体q臂上的APC、MCC和/或一个连锁基因的失活在一些上消化道癌症以及结肠癌和家族性腺瘤性息肉病的发病机制中发挥作用。
