Is cumulative frequency of mitochondrial DNA variants a biomarker for colorectal tumor progression?
Is cumulative frequency of mitochondrial DNA variants a biomarker for colorectal tumor progression?
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DOI：
10.1186/1476-4598-3-30
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发表时间：
2004-01-01
期刊：
影响因子：
37.3
通讯作者：
Go, Rodney
中科院分区：
文献类型：
--
作者：
Aikhionbare, Felix O.;Khan, Masood;Go, Rodney
为了研究线粒体DNA(MtDNA)改变与结直肠肿瘤发生的关系，我们使用高分辨限制性内切酶和测序技术分析了结直肠腺瘤的三种组织亚型(管状腺瘤8例、管状腺瘤9例和绒毛状腺瘤8例)、结直肠癌(CRC)组织27例及其周围正常组织(MSNT)52例的线粒体基因组。用9对重叠的引物对线粒体基因组进行扩增，并进行高分辨分析。DNA片段显示，与MSNT相比，三个腺瘤CRC之间的条带模式发生了变化，以确定mtDNA的变化。在这项研究中，总共观察到了38个生殖系mtDNA变种。38例中有22例被鉴定为突变，59%(13/22)为静止性突变，1例为1个碱基插入。13个SNPs中有16个位于限制性内切酶切点两侧，其中6个SNPs(37%)未见报道。这些突变/SNP大多是同质的，分布在线粒体基因的不同区域，包括16S和12S rRNA。根据我们的结果，随着腺瘤CRC的进展，mtDNA胚系变异的患病率增加。据我们所知，这是第一份表明线粒体基因变异在结直肠癌发生中的流行程度增加的报告。
To examine the relationship between mitochondrial DNA (mtDNA) alterations and colorectal tumorigenesis, we used high-resolution restriction endonucleases and sequencing to assess the mitochondrial genome from three histologic subtypes of colorectal adenomas (tubular = 8; tubulovillous = 9; and villous = 8), colorectal cancer (CRC) tissues = 27, and their matched surrounding normal tissue (MSNT) = 52. The mitochondrial genomes were amplified using 9 pairs of overlapping primers and systematically analyzed by means of high-resolution analysis. DNA fragments showing a shift in banding patterns between the three adenomas, CRC, in comparison to the MSNT were sequenced to identify the mtDNA alterations. A total of thirty-eight germ-line mtDNA variants were observed in this study. Twenty-two of the thirty-eight were identified as mutations and 59% (13 of 22) were silent mutations and one was a 1-bp insertion. Sixteen of thirtyeight were distinct SNPs in flanking regions of the restriction sites and, 6 of the 16 (37%) SNPs were not previously reported. Most of these mutations/SNPs were homoplasmic and distributed in various regions of mitochondrial genes including the 16S and 12S rRNA. Based on our results, mtDNA germline variants increased in prevalence with adenoma CRC progression. To the best of our knowledge, this is the first report to show an increased prevalence of mitochondrial gene variants in CRC tumorigenesis.