卵巢癌血清DNA3号染色体短臂基因杂合性丢失的研究

Loss of heterozygosity at chromosome 3p14,25 in serum DNA from ovarian cancer patients

目的 探讨血清DNA 3号染色体短臂 (3p1 4 ,2 5)等位基因杂合性丢失与卵巢癌发生、发展的相关性。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 38例卵巢癌及8例卵巢良性肿瘤患者的血清DNA 3p1 4 ,2 5的 4个微卫星位点 (D3S1 0 2 9、D3S1 2 2 8、D3S1 30 0、D3S1 4 81 )杂合性丢失进行检测。另外 ,检测 38例中 1 8例患者的组织及相应血清DNA 3p1 4 ,2 5杂合性丢失。结果 1 8例卵巢癌血清与肿瘤组织DNA 3p1 4 ,2 5基因 4个微卫星位点杂合性丢失率之间存在明显的相关性 (P <0 0 5)。 38例血清DNA标本中有 2 9例 (76 % )至少在 1个微卫星位点出现杂合性丢失 ,1 7例(45 % )有 2个以上微卫星位点出现杂合性丢失。卵巢癌Ⅱ期、Ⅲ期、Ⅳ期出现杂合性丢失率分别为 2 /4、78%、8/ 9。卵巢癌病理类型仅在微卫星D3S1 0 2 9位点的杂合性丢失率比较 ,差异有显著性 (P=0 0 0 74)。8例良性肿瘤组织及血清均未出现杂合性丢失。结论 卵巢癌患者血清DNA与肿瘤组织DNA 3p1 4 ,2 5出现杂合性丢失密切相关 ,血清 3p1 4 ,2 5出现杂合性丢失率与卵巢癌恶性程度有关。

Objective Investigate the frequency of loss of heterozygosity (LOH) at chromosome arm the short arm chromosome 3p14,25 in the serum DNA from ovarian cancer and its clinical application Methods Thirty eight ovarian cancer serum samples with 18 corresponding tumor tissues and 8 benign ovarian tumors were obtained,and DNA samples extracted from serum and tissue were examined for 3p14,25 LOH by using of polymerase chain reaction with four polymorphic microsatellite markers (D3S1029, D3S1228, D3S1300, D3S1481) Results Matched serum and tissue DNAs from 18 ovarian cancer patients showed significant concordance of 3p14,25 LOH ( P <0 05) 3p14,25 LOH in at least one of four loci occurred in 29 out of 38 (76%) serum samples, while 17 serum samples (45%) exhibited LOH at more than one locus According to International Federation of Gynecology and Obstetrics (FIGO) staging, there was a trend that the rate of LOH was higher in advanced stages, and the frequency of loss in stageⅡ?Ⅲ?Ⅳ was 2/4?78%?8/9 respectively It was also found that the number of microsatellite markers with 3p14,25 LOH was increased with tumor progressed No significant association of pathological types with LOH in serum DNA could be demonstrated except at locus D3S1029 Conclusions Since the strong correlation of 3p14,25 LOH between serum DNA and tumor tissue DNA, as well as the frequency of 3p14,25 LOH associated with malignancy of ovarian cancer, it is suggested that detection of serum DNA 3p14,25 LOH may be used as a molecular marker for staging and monitoring human ovarian cancer