Jiang X, Hitchcock A, Bryan E J, Watson R H, Englefield P, Thomas E J, Campbell I G
Obstetrics and Gynaecology, University of Southampton, United Kingdom.
Cancer Res. 1996 Aug 1;56(15):3534-9.
Endometriosis is a very common gynecological condition in which tissue similar to endometrium proliferates at sites outside the uterine cavity, most commonly the ovary. Although it generally remains a benign condition, malignant transformation has been documented. and it is commonly found in association with endometrioid subtype ovarian cancer. Tumor suppressor genes are commonly altered in ovarian cancers, and the development of endometriosis may involve mutations in the same class of genes. We have investigated this possibility by examining DNA from 40 cases of endometriosis for clonal status, alterations in TP53 and RASK, and allelic losses at candidate ovarian tumor suppressor loci on chromosome arms 6q, 9p, l1q, 17p, l7q, and 22q. The majority of endometriotic cysts were monoclonal, but interestingly, 8 of 10 normal endometrial glands were also monoclonal, demonstrating that both are able to develop from a single progenitor cell. No mutations were detected in TP53 or RASK. Loss of heterozygosity (LOH) was detected on chromosomes 9p (18%), 1lq (18%), and 22q (15%). In total, 11 of 40 (28%) cases demonstrated LOH at one or more of these loci. This study, which is the first to report LOH in endometriosis, supports the notion that tumor suppressor gene inactivation may play a role in the development of at least a subset of cases.
子宫内膜异位症是一种非常常见的妇科疾病，其中类似于子宫内膜的组织在子宫腔外的部位增殖，最常见于卵巢。尽管它通常仍是一种良性疾病，但已有恶变的记录，并且它常与子宫内膜样亚型卵巢癌相关。肿瘤抑制基因在卵巢癌中通常会发生改变，子宫内膜异位症的发生可能涉及同一类基因的突变。我们通过检测40例子宫内膜异位症病例的DNA来研究这种可能性，检测内容包括克隆状态、TP53和RASK的改变以及6号染色体长臂、9号染色体短臂、11号染色体长臂、17号染色体短臂、17号染色体长臂和22号染色体短臂上候选卵巢肿瘤抑制基因座的等位基因缺失。大多数子宫内膜异位囊肿是单克隆的，但有趣的是，10个正常子宫内膜腺体中有8个也是单克隆的，这表明两者都能够从单个祖细胞发育而来。在TP53或RASK中未检测到突变。在9号染色体短臂（18%）、11号染色体长臂（18%）和22号染色体短臂（15%）上检测到杂合性缺失（LOH）。在40例病例中，共有11例（28%）在这些基因座中的一个或多个上表现出LOH。这项首次报道子宫内膜异位症中存在LOH的研究支持了肿瘤抑制基因失活可能在至少一部分病例的发生中起作用这一观点。
