结直肠癌患者瘤内线粒体DNA非编码区突变异质性研究  

Intratumoralheterogeneity of non coding region of mitochondria DNA in patients with colorectal cancer

作　　者：张惠锋[1] 王华伟[2] 谢振荣[3] 任莉[4] 徐玉[5] 刘为军[6] 王昆华[5] ZHANG Hui-feng;WANG Hua-wei;XIE Zhen-rang;REN Li;XU Yu;LIU Wei-jun;WANG Kun-hua(First People's Hospital of Yunnan Province ,Affiliated Hospital of Kunming Science and Engineering University , Kunming 650000,P. R. China;First A ffiliated Hospital of Kunming Medical University ,Kunming 650000, P. R. China)

机构地区：[1]云南省第一人民医院,昆明理工大学附属医院临床药学科,云南昆明650000 [2]昆明医科大学第一附属医院生殖科,云南昆明650000 [3]昆明医科大学第一附属医院科教部,云南昆明650000 [4]云南省第一人民医院,昆明理工大学附属医院妇产科,云南昆明650000 [5]昆明医科大学第一附属医院普外科,云南昆明650000 [6]云南省第一人民医院,昆明理工大学附属医院肛肠科,云南昆明650000

出　　处：《中华肿瘤防治杂志》2019年第7期473-478,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81660094);昆明医科大学联合专项(2015FB100)

摘　　要：目的线粒体DNA非编码区是调控线粒体DNA复制和转录的重要区域,由于其自身的结构特点,具有较高的突变速率,本研究旨在探讨结直肠癌(colorectal cancer,CRC)瘤内不同空间位置线粒体DNA非编码区的突变异质性情况。方法收集2013-08-01-2014-10-31云南省第一人民医院普外科手术治疗的26例CRC患者瘤内不同空间位置的78例肿瘤组织和26例癌旁正常组织。采用HE染色法,显微镜下确定肿瘤组织的类型;直接测序法对线粒体DNA非编码区进行测序,比较CRC瘤内不同空间位置的线粒体DNA非编码区的突变情况。结果有10例CRC患者mtDNA D-loop区发生了突变,突变率为45.5%。突变位点分别为HVSI的16114、16166、16248、16278、16304、16362及16390位点,其中309点位点突变最多,有2例同时在HVSⅠ、Ⅱ和Ⅲ有突变,其余患者均只发生了一个位点突变。有9例存在瘤内mtDNA非编码区突变的异质性。结论 CRC患者mtDNA非编码区的突变存在瘤内异质性。OBJECTIVE The non coding region of mitochondrial DNA is an important region regulating the replication and transcription of mitochondrial DNA.Because of its structural characteristics,it has a high mutation rate.The objective of this study was to explore the intratumoral mutation of colorectal cancer in the non coding region of mitochondria DNA.METHODS We analyzed 78 tumor tissue samples from 26 patients with CRC,and 26 adjacent normal tissue samples of them were collected.The patients received surgicsl treatmens in the department of general surgury of the First People’s Hospital of Yunnan Province from August,2018 to October,2014.HE determined the type of tumor tissue under microscope.The sanger sequencing method was used to sequence the non coding region of mitochondrial DNA,and comparing the mutation in different locations of CRC tumor.RESULTS Ten cases(45.5%)had mutations in the mtDNA D-loop region.The mutation sites were HVS Ⅰ 16114,16166,16248,16278,16304,16362,and 16390.The most polular mutation site was 309.Simultaneous mutations in HVSⅠ,Ⅱ and Ⅲ were identified in 2 cases.Among 10 patients with mtDNA D-loop mutations,9 cases showed intra-tumor heterogeneity.CONCLUSION The genic mutation has the intratumoral heterogeneity in the non coding region of mitochondria DNA in colorectal cancer.

关 键 词：结直肠癌 线粒体DNA 非编码区 异质性 

分 类 号：R735.3[医药卫生—肿瘤]