Thomas G
Laboratoire de Genetique des Tumeurs, Institut Curie, Paris, France.
Curr Opin Oncol. 1994 Jul;6(4):406-12. doi: 10.1097/00001622-199407000-00014.
Fascinating progress has been made in the past 2 years in our understanding of the genetic alterations associated with colorectal cancer predisposition and development. First, the genotype-phenotype relationship of the cancer susceptibility syndrome associated with familial adenomatous polyposis has been shown to depend on mutation type. Second, hereditary nonpolyposis colorectal cancer syndromes have been recognized as being frequently associated with a defect in the DNA mismatch-repair pathway. A gene on chromosome 2 called hMSH2, which demonstrates homology with the bacterial repair gene MutS, has been shown to be altered in some families with hereditary nonpolyposis colorectal cancer. A defect on chromosome 3 may act by impairing the same pathway. Genotyping of particular loci, termed microsatellite, provides an easy identification of tumors deficient in mismatch repair. Third, the mechanisms by which the inactivation of tumor-suppressor genes such as p53 and APC may contribute to the tumorigenic process have begun to be elucidated. These different discoveries will have important impacts in the prevention and management of colorectal carcinoma, one of the most frequent human cancers.
在过去两年里，我们对与结直肠癌易感性和发展相关的基因改变的理解取得了引人注目的进展。首先，已表明与家族性腺瘤性息肉病相关的癌症易感性综合征的基因型-表型关系取决于突变类型。其次，遗传性非息肉病性结直肠癌综合征已被认为常与DNA错配修复途径缺陷有关。在2号染色体上有一个名为hMSH2的基因，它与细菌修复基因MutS具有同源性，在一些遗传性非息肉病性结直肠癌家族中已显示该基因发生了改变。3号染色体上的一个缺陷可能通过损害同一途径起作用。对特定基因座（称为微卫星）进行基因分型，可轻松识别错配修复缺陷的肿瘤。第三，诸如p53和APC等肿瘤抑制基因的失活可能促成肿瘤发生过程的机制已开始得到阐明。这些不同的发现将对结直肠癌（人类最常见的癌症之一）的预防和管理产生重要影响。
