Department of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC.
Oncol Rep. 2012 Jul;28(1):69-76. doi: 10.3892/or.2012.1761. Epub 2012 Apr 10.
We investigated the microsatellite alterations in mitochondrial DNA (mtDNA) and in TP53 in thoracic esophageal squamous cell carcinomas (TESCC). Using laser microdissection, 66 paired non-cancerous esophageal muscles, non-cancerous esophageal mucosa, cancerous TESCC nests plus 35 metastatic lymph nodes harvested from 66 resected esophagi of TESCC patients were subjected to DNA extraction. D310 and D17S960 were chosen as markers to address microsatellite alterations in mtDNA, including changes in copy number and homoplasmic/heteroplasmic mutations of mtDNA, and in TP53, including loss of heterozygosity (LOH) and microsatellite instability (MI). From non-cancerous esophageal mucosa to cancerous TESCC nests and then metastatic lymph nodes, a trend of homoplasmic D310 mutation (10.6, 25.8, 31.4%; p=0.023), an ever increase of mtDNA copy ratios (0.892, 1.128, 1.183; p=0.018) and an elevated incidence of TP53 LOH (19.7, 34.8, 37.1%; p=0.010) were observed. From T1, T2, T3 to T4 TESCC, the incidence of TP53 LOH (12.5, 16.7, 34.8, 52.2%; p=0.011) was increased, in a stepwise fashion. Furthermore, we observed an association of TP53 LOH with an increased mtDNA copy ratio (p=0.022) and TP53 MI with heteroplasmic D310 mutation (p=0.069) in TESCC. Concurrent and associated microsatellite alterations in mtDNA and in TP53 in TESCC support the cancer clonal expansion theory and imply a possible relationship between the mitochondria and p53 in TESCC.
我们研究了胸段食管鳞癌（TESCC）中线粒体 DNA（mtDNA）和 TP53 的微卫星改变。使用激光微切割，对 66 例 TESCC 患者切除的食管中 66 对非癌性食管肌肉、非癌性食管黏膜、癌性 TESCC 巢以及 35 个转移性淋巴结进行 DNA 提取。选择 D310 和 D17S960 作为标记，以检测 mtDNA 的微卫星改变，包括 mtDNA 拷贝数的变化和同质/异质突变，以及 TP53 的杂合性丢失（LOH）和微卫星不稳定性（MI）。从非癌性食管黏膜到癌性 TESCC 巢，再到转移性淋巴结，同质 D310 突变（10.6%、25.8%、31.4%；p=0.023）、mtDNA 拷贝比的不断增加（0.892、1.128、1.183；p=0.018）和 TP53 LOH 发生率的升高（19.7%、34.8%、37.1%；p=0.010）都呈递增趋势。从 T1、T2、T3 到 T4 TESCC，TP53 LOH 发生率（12.5%、16.7%、34.8%、52.2%；p=0.011）呈递增趋势。此外，我们观察到在 TESCC 中，TP53 LOH 与 mtDNA 拷贝比的增加相关（p=0.022），TP53 MI 与同质 D310 突变相关（p=0.069）。TESCC 中线粒体 DNA 和 TP53 中同时发生和相关的微卫星改变支持肿瘤克隆扩张理论，并暗示了线粒体和 p53 之间在 TESCC 中的可能关系。
