人卵巢癌3号染色体短臂杂合性丢失的研究

目的探讨3号染色体短臂(3p14)等位基因杂合性丢失(10ss 0f heterozygosity,LOH)与人卵巢癌发生及发展之间的相关性研究.方法采用聚合酶链反应并结合二核苷酸重复序列多态性方法,分别对31例卵巢癌及24例卵巢良性肿瘤患者的组织标本DNA中3p14上3个微卫星位点(D3S1234、D3S1300、D3S1312)杂合性丢失(LOH)进行检测,同时还随机地检测31例卵巢癌中21例患者的血清DNA中3p14的LOH.结果31例卵巢癌组织DNA中21例(67.7%)至少在1个微卫星位点中出现杂合性丢失,11例卵巢癌患者(35.5%)有2个以上微卫星位点出现LOH.癌组织DNA中基因杂合性丢失频率与癌细胞分化程度呈正相关,与肿瘤病理类型及FIGO分期无关.24例卵巢良性肿瘤组织及血清DNA中均未出现3p位点上的杂合性丢失.21例卵巢癌血清DNA与肿瘤组织DNA 3p14基因3个微卫星位点杂合性丢失率之间存在明显的相关性(P＜0 05).结论鉴于人卵巢癌3p14出现杂合性丢失率与其癌细胞分化恶性程度相关以及卵巢癌患者血清DNA与癌组织DNA中3p14出现LOH相一致,故本文实验结果提示3p14 LOH的检测可能具有对卵巢癌患者的临床诊断潜在性价值.

The loss of heterozygosity(LOH) on chromosome 3 in the DNA samples from human ovarian cancer

Objective To investigate the frequency of the loss of heterozygosity(LOH) on chromosome 3(3p14 )in the DNA samples from human ovarian cancer tissues and sera. Methods There were totally 76 DNA samples extracted from 31 ovarian cancer tissues, 21 corresponding serum samples of patients with ovarian cancer and 24 benign ovarian tumor tissues to be examined for LOH of 3pl4 by using of PCR with three polymorphic microsatellite markers (D3S1234,D3S1300,D3S1312). Results LOH of 3pl4 occurred in 21 of 31(71. 0%) cancer samples with at least one locus, while LOH with more then one locus in 11 tissue samples(35. 5). The frequency of LOH at 3pl4 correlated with differentiation grade of tumors, such as that LOH was present in 92. 9% (13 of 14)of G3 tumors but only 52. 9%(9 of 17) of G1/G2 tumors ( P <0. 05). No association between histological type and cancer stages was found in frequency of LOH. LOH at 3P14 were significantly concordant in matched serum and tissue DNA from 21 ovarian cancer patients(P<0. 05). LOH was not observed in tissue or sera DNA samples of 24 patients with benign ovarian tumors. Conclusion Since the frequency of 3pl4 LOH is associated with malignancy of ovarian cancer and strongly correlated in both serum DNA and tumor tissue DNA, it is suggested that the detection of LOH at 3p may be used as a potential tumor marker for the diagnosis of ovarian cancer.