發(fā)布時間：2018-04-09 16:05

  本文選題：乳腺腫瘤　切入點：微衛(wèi)星不穩(wěn)定(MSI)　出處：《貴州醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:通過檢測乳腺導(dǎo)管上皮普通型增生(usual ductal hyperplasia,UDH)、乳腺導(dǎo)管非典型增生(atypical ductal hyperplasia,ADH),乳腺導(dǎo)管原位癌(ductal carcinoma in situ,DCIS)及乳腺浸潤性導(dǎo)管癌(invasive ductal carcinoma,IDC)中染色體16q、17p微衛(wèi)星不穩(wěn)定(microsatellite instability,MSI)與雜合性缺失(loss of heterozygosity,LOH)的發(fā)生頻率及p53、CDH13基因啟動子的異常甲基化,嘗試發(fā)現(xiàn)從UDH發(fā)展為IDC的重要分子生物學(xué)標(biāo)志。方法:通過PCR-SSCP方法來檢測101例乳腺病變(其中UDH 31例,ADH 10例,DCIS32例,IDC 28例)中染色體16q、17p上13個微衛(wèi)星位點的LOH/MSI發(fā)生情況;甲基化特異性PCR(MS-PCR)及瓊脂糖凝膠電泳法來檢測其p53、CDH13基因啟動子的異常甲基化發(fā)生情況。結(jié)果:101例標(biāo)本中所有位點均有一定程度的LOH/MSI發(fā)生,且DCIS及IDC中的發(fā)生頻率要高于UDH組(P0.05)。染色體16q23區(qū)域的D16S515、D16S507、D16S422,17p12及17p13區(qū)域的D17S261、D17S654,LOH/MSI發(fā)生總頻率分別為31.7%、21.8%、30.7%、25.7%、22.8%(P0.05),進(jìn)一步兩兩比較后可知在D16S507和D16S515上UDH組的LOH/MSI的發(fā)生頻率明顯低于ADH組、DCIS組和IDC組(P0.05);D17S654和D16S422上UDH組的LOH/MSI的發(fā)生頻率明顯低于DCIS組和IDC組(P0.05);D17S261上UDH組的LOH/MSI的發(fā)生頻率明顯低于IDC組(P0.05)。在IDC組中,16q與17p染色體上的MS發(fā)生LOH/MSI頻率改變顯著相關(guān)。在UDH中p53和CDH13基因的啟動子區(qū)域的CpG島異常甲基化發(fā)生率較低,并且p53基因啟動子異常甲基化在乳腺癌患者中其發(fā)生頻率明顯高于UDH組和ADH組(P0.05);CDH13基因啟動子異常甲基化的發(fā)生頻率在乳腺癌患者中明顯高于UDH組(P0.05)。在UDH組和IDC組中,染色體發(fā)生LOH/MSI與p53基因啟動子甲基化成正相關(guān)性(P0.05);在UDH組與IDC組中染色體發(fā)生LOH/MSI與CDH13基因啟動子甲基化顯著相關(guān)(P0.05)。p53、CDH13基因啟動子的異常甲基化發(fā)生時,四組乳腺病變中LOH/MSI發(fā)生頻率的比較差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論:位點D16S515、D16S507、D16S422和D17S654、D17S261發(fā)生LOH/MSI的改變可能在UDH發(fā)展為IDC中起到關(guān)鍵作用,是乳腺癌發(fā)生早期分子事件。抑癌基因p53的啟動子異常甲基化發(fā)生可能是參與UDH及ADH發(fā)展為IDC的早期分子事件。抑癌基因CDH13的啟動子異常甲基化發(fā)生可能成為UDH發(fā)展為IDC的重要分子生物學(xué)標(biāo)志之一。
[Abstract]:The frequency of loss of heterozygosity of heterozygosity and abnormal methylation of p53 CDH13 promoter.An important molecular biological marker from UDH to IDC was found.Methods: 13 microsatellite loci on chromosome 16qS17p were detected by PCR-SSCP method in 101 cases of breast lesions (including 31 cases of UDH and 10 cases of DCIS 32 cases of IDC).Methylation specific PCRS-PCR) and agarose gel electrophoresis were used to detect the abnormal methylation of p53 CDH13 gene promoter.Results there was a certain degree of occurrence of LOH/MSI at all loci in 10 ~ 1 samples, and the frequency of occurrence in DCIS and IDC was higher than that in UDH group (P 0.05).The incidence rate of LOH/MSI in UDH group was significantly lower than that in DCIS group and IDC group (P 0.05 P 17S261). The frequency of LOH/MSI in UDH group was significantly lower than that in IDC group (P 0.05).In IDC group, there was a significant correlation between the frequency of LOH/MSI and the frequency of LOH/MSI on chromosome 17p.The incidence of abnormal CpG island methylation in the promoter region of p53 and CDH13 genes in UDH was lower.The frequency of abnormal methylation of p53 promoter in breast cancer patients was significantly higher than that in UDH group and ADH group. The frequency of abnormal methylation of p53 promoter was significantly higher in breast cancer patients than that in UDH group.In UDH group and IDC group, there was a positive correlation between LOH/MSI and p53 promoter methylation, and in UDH group and IDC group, there was a significant correlation between LOH/MSI and CDH13 promoter methylation.There was no significant difference in the frequency of LOH/MSI among the four groups (P 0.05).Conclusion: the changes of LOH/MSI in D16S515D16S507, D16S422 and D17S654D17S261 may play a key role in the development of UDH into IDC, and may be an early molecular event in the development of breast cancer.The abnormal methylation of p53 promoter may be an early molecular event involved in the development of UDH and ADH into IDC.The abnormal methylation of CDH13 promoter may be one of the important molecular biological markers for the development of UDH into IDC.
【學(xué)位授予單位】：貴州醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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