Imyanitov E N, Birrell G W, Filippovich I, Sorokina N, Arnold J, Mould M A, Wright K, Walsh M, Mok S C, Lavin M F, Chenevix-Trench G, Khanna K K
Group of Molecular Diagnostics, N.N. Petrov Institute of Oncology, St.-Petersburg, 189646, Russia.
Oncogene. 1999 Aug 12;18(32):4640-2. doi: 10.1038/sj.onc.1202863.
Loss of heterozygosity (LOH) involving the distal part of the short arm of chromosome 1 occurs frequently in ovarian adenocarcinomas but the tumour suppressor gene(s) targeted by this event is unknown. We have used five microsatellite markers in a panel of 56 ovarian adenocarcinomas to determine which part of 1p34 - 36 is the focus of this LOH. LOH was considerably more common at 1p36 (43%) than at 1p34 - 35 (18%), and 11 tumours showed LOH at 1p36 but not at 1p34 - 35. These data strongly suggest the presence of a tumour suppressor gene inactivated in ovarian adenocarcinoma at 1p36. The p53 homologue, p73, has recently been isolated and mapped to 1p36 and therefore is a candidate for this tumour suppressor gene. However, RT - PCR and Western analyses revealed strong expression of p73 in ovarian adenocarcinoma cell lines but very low or undetectable levels in normal ovarian surface epithelial cells. Immunohistochemical analysis of primary ovarian tumours showed that only 3/22 (14%) contained p73 expressing cells. There was no association between 1p36 LOH and p73 expression in ovarian tumours, nor between p73 and p53 expression. These findings strongly suggest that p73 is not the target of 1p36 LOH in ovarian adenocarcinomas but indicate the presence of an, as yet unidentified, tumour suppressor gene in this region that plays an important role in ovarian tumorigenesis.
1号染色体短臂远端杂合性缺失（LOH）在卵巢腺癌中频繁发生，但该事件所靶向的肿瘤抑制基因尚不清楚。我们在一组56例卵巢腺癌中使用了5个微卫星标记，以确定1p34 - 36的哪一部分是这种LOH的焦点。1p36处的LOH（43%）比1p34 - 35处（18%）更为常见，并且有11个肿瘤在1p36处显示LOH，但在1p34 - 35处未显示。这些数据强烈提示在1p36处存在一个在卵巢腺癌中失活的肿瘤抑制基因。p53同源物p73最近已被分离并定位于1p36，因此是这个肿瘤抑制基因的一个候选者。然而，逆转录聚合酶链反应（RT - PCR）和蛋白质免疫印迹分析显示，p73在卵巢腺癌细胞系中强烈表达，但在正常卵巢表面上皮细胞中水平极低或无法检测到。对原发性卵巢肿瘤的免疫组织化学分析表明，仅3/22（14%）含有表达p73的细胞。在卵巢肿瘤中，1p36 LOH与p73表达之间没有关联，p73与p53表达之间也没有关联。这些发现强烈提示p73不是卵巢腺癌中1p36 LOH的靶点，但表明在该区域存在一个尚未确定的肿瘤抑制基因，它在卵巢肿瘤发生中起重要作用。
