Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas.
Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas.
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DOI：
10.1186/1472-6823-7-8
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发表时间：
2007-10-04
影响因子：
2.7
通讯作者：
Arnold A
中科院分区：
文献类型：
--
作者：
Costa-Guda J;Tokura T;Roth SI;Arnold A
线粒体 DNA (mtDNA) 突变在肿瘤发生中的潜在发病意义存在争议。我们假设，像人类甲状旁腺这样的缓慢复制组织的良性肿瘤发生可能构成一个特别肥沃的土壤，mtDNA突变赋予的选择性优势可以在其中表现出来，并可能有助于在甲状旁腺肿瘤亚群中观察到的嗜氧表型。我们通过对 30 个散发性甲状旁腺腺瘤（18 个主细胞和 12 个嗜酸细胞）、8 个独立的多克隆甲状旁腺原代主细胞增生加上相应的正常对照样本、5 个正常甲状旁腺和 1 个正常甲状腺中每一个的整个 16.6 kb 线粒体基因组进行测序来寻找获得性线粒体 DNA 突变。在所研究的 30 个甲状旁腺腺瘤中的 15 个（12 个嗜酸腺瘤中的 9 个，18 个主细胞腺瘤中的 6 个）中发现了 27 个体细胞突变。在增生的甲状旁腺中没有观察到体细胞突变。体细胞突变的特征表明它们可能具有选择性优势并有助于甲状旁腺腺瘤的分子发病机制。重要的是，嗜酸细胞与主细胞腺瘤的突变发生率存在统计学上的显着差异，这也表明线粒体DNA突变可能导致嗜酸细胞表型。
The potential pathogenetic significance of mitochondrial DNA (mtDNA) mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly replicating tissue like the human parathyroid might constitute an especially fertile ground on which a selective advantage conferred by mtDNA mutation could be manifested and might contribute to the oxyphilic phenotype observed in a subset of parathyroid tumors. We sought acquired mitochondrial DNA mutations by sequencing the entire 16.6 kb mitochondrial genome of each of thirty sporadic parathyroid adenomas (18 chief cell and 12 oxyphil cell), eight independent, polyclonal, parathyroid primary chief cell hyperplasias plus corresponding normal control samples, five normal parathyroid glands, and one normal thyroid gland. Twenty-seven somatic mutations were identified in 15 of 30 (9 of 12 oxyphil adenomas, 6 of 18 chief cell) parathyroid adenomas studied. No somatic mutations were observed in the hyperplastic parathyroid glands. Features of the somatic mutations suggest that they may confer a selective advantage and contribute to the molecular pathogenesis of parathyroid adenomas. Importantly, the statistically significant differences in mutation prevalence in oxyphil vs. chief cell adenomas also suggest that mtDNA mutations may contribute to the oxyphil phenotype.