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目的探讨化疗后卵巢癌组织中线粒体DNA的变化。方法收集2002年11月至2003年8月北京协和医院收治的7例初治和9例化疗后复发的卵巢癌患者的肿瘤组织及其周围的正常组织标本,对其线粒体DNA全长测序,与基因库中数据对比,确定基因库中未记载的新的多态性变化位点和突变位点。结果共发现69个新的多态性变化位点和17个突变位点,多态性变化在初治和复发卵巢癌患者的肿瘤组织和周围的正常组织中均存在,而突变仅在其肿瘤组织中存在。初治标本多态性变化位点平均2.7个,复发标本平均5.6个,两者比较,差异有统计学意义(P=0.01)。初治标本中编码蛋白的多态性变化位点为14个,其中3个(21%)引起了氨基酸的改变;复发标本中编码蛋白的多态性变化位点为41个,其中13个(32%)引起了氨基酸的改变,两者氨基酸改变的发生率比较,差异无统计学意义(P=0.700)。初治标本的突变率为5/7,突变位点有7个,其中处于蛋白编码区的4个突变位点中有3个(3/4)引起了氨基酸的改变;复发标本的突变率为5/9,突变位点有10个,其中处于蛋白编码区的5个突变位点全部(5/5)使氨基酸发生了改变,两者突变率和突变位点引起的氨基酸改变发生率比较,差异均无统计学意义(P>0.05)。结论化疗后复发的卵巢癌组织中,线粒体DNA的多态性变化明显增加,而线粒体DNA的突变无明显增加。提示线粒体DNA突变可能是肿瘤固有的特性之一。
Objective To investigate the changes of mitochondrial DNA in ovarian cancer after chemotherapy. Methods Tumor tissue and normal tissue samples from 7 patients with primary and 9 patients with ovarian cancer who relapsed after chemotherapy were collected from Peking Union Medical College Hospital from November 2002 to August 2003. The full length of mitochondrial DNA was sequenced, Comparison of the data in the gene pool to identify new unrecorded polymorphic sites and mutations in the gene pool. Results A total of 69 new polymorphic sites and 17 mutations were found. Polymorphic changes were found in the tumor tissues and surrounding normal tissues in both newly diagnosed and recurrent ovarian cancer patients. However, mutations were only found in the tumors There is in the organization. The average number of polymorphic sites in newly diagnosed specimens was 2.7, and the average number of recurrence specimens was 5.6. The difference between the two groups was statistically significant (P = 0.01). There were 14 polymorphic loci in newly diagnosed specimens, of which 3 (21%) caused amino acid changes. The number of polymorphic sites in the recurrent specimens was 41, of which 13 32%) caused a change in amino acids, the difference between the two amino acid changes, the difference was not statistically significant (P = 0.700). The mutation rate was 5/7 in the untreated specimens and 7 in the mutation sites. Three of the four mutation sites (3/4) in the protein coding region caused amino acid changes. The mutation rate of the recurrent specimens was 5/9, there are 10 mutation sites, of which 5 (5/5) in the coding region of the protein all changed the amino acids, the mutation rates of the two and the amino acid changes caused by the mutation sites were compared, There was no significant difference (P> 0.05). Conclusion The changes of mitochondrial DNA polymorphisms in ovarian cancer recurrence after chemotherapy were significantly increased, while the mitochondrial DNA mutations were not significantly increased. Suggest that mitochondrial DNA mutations may be one of the inherent characteristics of the tumor.