Khine K, Smith D R, Goh H S
Department of Colorectal Surgery, Singapore General Hospital.
Cancer. 1994 Jan 1;73(1):28-35. doi: 10.1002/1097-0142(19940101)73:1<28::aid-cncr2820730107>3.0.co;2-3.
Colorectal cancers often show allelic loss of chromosomes 5q and 17p, regions where the tumor suppressor genes p53 and adenomatous polyposis coli are known to reside. Currently, the inactivation of tumor suppressor genes and the activation of oncogenes are considered major events involved in tumor development. According to a recent genetic model, ras gene mutations and allelic deletion of chromosome 5q are early changes, whereas chromosome 17p and 18q deletions are late changes in colorectal tumorigenesis. It has been shown that 17p and 18q deletions are associated with an increased tendency of disease dissemination in colorectal cancer. Most of the studies on allelic deletion in colorectal cancer were undertaken with Western population cohorts. The authors examined the association of chromosomes 5q and 17p deletions with clinical parameters, including metastasis in a predominantly Chinese population with a high incidence of colorectal cancer.
Allelic deletion was studied with the restriction fragment length polymorphism technique in tumors from 102 and 100 sporadic colorectal cancer cases for chromosomes 5q and 17p, respectively. Probes pi 227 and ECB27 were used for chromosome 5q, and probe YNZ22.1 was used for chromosome 17p.
5q Deletion was found in 33% of informative cases, whereas 17p deletion was seen in 69% of informative cases. 17p Allelic loss showed significant association with Dukes' Stage D as well as the presence of distant metastasis, whereas 5q deletion showed no such association.
Allelic loss on chromosome 17p may be a useful prognostic marker in cases of colorectal cancer.
结直肠癌常表现出5号染色体长臂(5q)和17号染色体短臂(17p)的等位基因缺失,已知肿瘤抑制基因p53和腺瘤性息肉病基因位于这些区域。目前,肿瘤抑制基因的失活和癌基因的激活被认为是肿瘤发生中的主要事件。根据最近的遗传模型,ras基因突变和5号染色体长臂等位基因缺失是早期变化,而17号染色体短臂和18号染色体长臂缺失是结直肠癌发生过程中的晚期变化。研究表明,17号染色体短臂和18号染色体长臂缺失与结直肠癌疾病播散倾向增加有关。大多数关于结直肠癌等位基因缺失的研究是在西方人群队列中进行的。作者在结直肠癌高发的主要为中国人群中,研究了5号染色体长臂和17号染色体短臂缺失与包括转移在内的临床参数之间的关联。
分别采用限制性片段长度多态性技术,对102例和100例散发性结直肠癌病例的肿瘤进行5号染色体长臂和17号染色体短臂的等位基因缺失研究。探针pi 227和ECB27用于5号染色体长臂,探针YNZ22.1用于17号染色体短臂。
在有信息的病例中,33%发现有5号染色体长臂缺失,而69%发现有17号染色体短臂缺失。17号染色体短臂等位基因缺失与Dukes D期以及远处转移的存在显著相关,而5号染色体长臂缺失则无此关联。
17号染色体短臂的等位基因缺失可能是结直肠癌病例中一个有用的预后标志物。