Wang Zhaoxi, Choi Sojung, Lee Jinseon, Huang Yen-Tsung, Chen Feng, Zhao Yang, Lin Xihong, Neuberg Donna, Kim Jhingook, Christiani David C
Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
Department of Thoracic Surgery, Samsung Medical Center, Seoul, Korea.
Cancer Inform. 2015 Jan 27;14(Suppl 1):1-9. doi: 10.4137/CIN.S13976. eCollection 2015.
Mutations in the mtDNA genome have long been suspected to play an important role in cancer. Although most cancer cells harbor mtDNA mutations, the question of whether such mutations are associated with clinical prognosis of lung cancer remains unclear. We resequenced the entire mitochondrial genomes of tumor tissue from a population of 250 Korean patients with non-small cell lung cancer (NSCLC). Our analysis revealed that the haplogroup (D/D4) was associated with worse overall survival (OS) of early-stage NSCLC [adjusted hazard ratio (AHR), 1.95; 95% CI, 1.14-3.33; P trend = 0.03]. By comparing the mtDNA variations between NSCLC tissues and matched blood samples, we found that haplogroups M/N and/or D/D4 were hotspots for somatic mutations, suggesting a more complicated mechanism of mtDNA somatic mutations other than the commonly accepted mechanism of sequential accumulation of mtDNA mutations.
长期以来，人们一直怀疑线粒体DNA（mtDNA）基因组中的突变在癌症中起重要作用。尽管大多数癌细胞都存在mtDNA突变，但这些突变是否与肺癌的临床预后相关仍不清楚。我们对250名韩国非小细胞肺癌（NSCLC）患者群体的肿瘤组织的整个线粒体基因组进行了重测序。我们的分析表明，单倍群（D/D4）与早期NSCLC患者更差的总生存期（OS）相关[调整后的风险比（AHR）为1.95；95%置信区间（CI）为1.14 - 3.33；P趋势 = 0.03]。通过比较NSCLC组织与匹配的血液样本之间的mtDNA变异，我们发现单倍群M/N和/或D/D4是体细胞突变的热点，这表明mtDNA体细胞突变的机制比普遍接受的mtDNA突变顺序积累机制更为复杂。
