Thomas E J, Campbell I G
Department of Obstetrics and Gynaecology, University of Southampton, Princess Anne Hospital, Southampton, UK.
Gynecol Obstet Invest. 2000;50 Suppl 1:44-50. doi: 10.1159/000052878.
In a series of studies, we have hypothesised that endometriotic proliferation is, in part, precipitated by mutations in oncogenes or deletions in tumor suppressor genes that have been shown to be important steps in the transformation from a benign to a malignant epithelium. We reported previously that we could find no mutations in the TP53 and RASK genes in cases of endometriosis. However, having shown that endometriotic deposits were monoclonal, we showed loss of heterozygosity on chromosomes 9p (18%), 11q (18%), and 22q (15%) - in total 28% of endometriotic lesions showed loss of heterozygosity at one or more sites [1]. We could not demonstrate any loss of heterozygosity in normal endometrium. We examined adjacent endometriosis, atypical endometriosis, and endometrioid carcinoma of the ovary and showed common genetic alterations that are consistent with a common lineage. These common alterations were not seen in lesions that were distant from each other [2]. In endometrioid tumors, we reported an increased frequency of mutations in the PTEN/MMAC tumor suppressor genes that was not seen in clear cell or serous carcinoma, suggesting distinct developmental pathways for these tumors [3].
在一系列研究中，我们提出假说，认为子宫内膜异位症的增殖部分是由癌基因的突变或肿瘤抑制基因的缺失所引发的，这些已被证明是从良性上皮向恶性上皮转变的重要步骤。我们之前报道过，在子宫内膜异位症病例中，未发现TP53和RASK基因的突变。然而，在证实子宫内膜异位沉积物为单克隆性之后，我们发现9号染色体短臂（18%）、11号染色体长臂（18%）和22号染色体长臂（15%）存在杂合性缺失——总计28%的子宫内膜异位病变在一个或多个位点显示杂合性缺失[1]。我们在正常子宫内膜中未发现任何杂合性缺失。我们检查了相邻的子宫内膜异位症、非典型子宫内膜异位症以及卵巢子宫内膜样癌，发现它们存在共同的基因改变，这与共同的谱系一致。这些共同改变在彼此距离较远的病变中未出现[2]。在子宫内膜样肿瘤中，我们报道了PTEN/MMAC肿瘤抑制基因的突变频率增加，而在透明细胞癌或浆液性癌中未观察到这种情况，这表明这些肿瘤具有不同的发展途径[3]。
