Eccles D M, Russell S E, Haites N E, Atkinson R, Bell D W, Gruber L, Hickey I, Kelly K, Kitchener H, Leonard R
ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
Oncogene. 1992 Oct;7(10):2069-72.
We have studied 146 ovarian tumours (94 carcinomas, 22 tumours of low malignant potential and 30 benign tumours) for evidence of allele loss on chromosome 17p and 17q sufficient to imply the proximity of a tumour-suppressor gene. We have examined two polymorphic loci (YNZ22.2 and BHP53) on 17p13 and one on chromosome 17q (17q23-qter). Loss of heterozygosity (LOH) was detected in 34/63 (54%) informative malignant tumours at YNZ22.2 and 22/47 (47%) at BHP53; on 17q, 45/64 (70%) had LOH. Allele loss was detected in a small number of benign and borderline tumours. There was a statistically significant difference between the patterns of allele loss in serous and endometrioid groups of tumours, and allele loss occurred with significantly greater frequency on 17q than on 17p. Comparison of all malignant tumours presenting with either localized (FIGO stage I/II) or widespread (FIGO stage III/IV) disease showed that, particularly on 17q, allele loss increases in the more advanced stages. The p53 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter. Loss of function in this gene may be responsible for the frequently observed rapid progression of serous-type adenocarcinomas to an advanced stage.
我们研究了146例卵巢肿瘤（94例癌、22例低恶性潜能肿瘤和30例良性肿瘤），以寻找17号染色体短臂（17p）和长臂（17q）上等位基因缺失的证据，这种缺失足以提示存在一个肿瘤抑制基因。我们检测了17p13上的两个多态性位点（YNZ22.2和BHP53）以及17号染色体上17q23 - qter区域的一个位点。在YNZ22.2位点，63例信息充分的恶性肿瘤中有34例（54%）检测到杂合性缺失（LOH）；在BHP53位点，47例中有22例（47%）检测到LOH；在17q上，64例中有45例（70%）存在LOH。在少数良性和交界性肿瘤中也检测到了等位基因缺失。浆液性和子宫内膜样肿瘤组的等位基因缺失模式存在统计学显著差异，且17q上等位基因缺失的频率显著高于17p。对所有表现为局限性（国际妇产科联盟（FIGO）分期I/II期）或广泛性（FIGO分期III/IV期）疾病的恶性肿瘤进行比较发现，尤其是在17q上，等位基因缺失在疾病较晚期更为常见。p53肿瘤抑制基因与卵巢癌发生有关，我们的研究结果提示，一个重要的肿瘤抑制基因可能位于17q23 - qter区域。该基因功能缺失可能是浆液性腺癌常见的快速进展至晚期的原因。
