Mitochondrial DNA mutation in normal margins and tumors of recurrent head and neck squamous cell carcinoma patients.
Mitochondrial DNA mutation in normal margins and tumors of recurrent head and neck squamous cell carcinoma patients.
复制标题
DOI：
10.1158/1940-6207.capr-10-0018
复制
发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Koch WM
中科院分区：
文献类型：
--
作者：
Dasgupta S;Koch R;Westra WH;Califano JA;Ha PK;Sidransky D;Koch WM
线粒体DNA（mtDNA）突变报告原发性头颈部鳞状细胞癌（HNSCC）患者。然而，很少有信息是关于mtDNA突变模式在组织学阴性的手术切缘和肿瘤的HNSCC患者谁经历了肿瘤复发。本研究旨在了解组织学阴性切缘和随访期间发生局部复发的HNSCC患者肿瘤中mtDNA突变的性质和时间。对50名复发性HNSCC患者的匹配正常淋巴细胞、组织学正常边缘和肿瘤中的完整16.5 kb线粒体基因组进行了测序。然后将mtDNA突变与临床参数进行比较。48%（24/50）的患者在肿瘤中至少有一个体细胞mtDNA突变，共检测到37个体细胞mtDNA突变。线粒体DNA突变主要是异质性的性质和核苷酸转换（A参与G; T参与C）。46%的突变（37个中的17个）在肿瘤中检测到，并且在患者的相应组织学正常边缘中也可检测到。mtDNA突变涉及mtDNA的编码区和非编码区。大多数（17个中的9个，53%）非编码突变涉及tRNA。75%（15/20）的编码mtDNA突变本质上是非同义的，主要影响细胞色素c氧化酶（复合物IV），在不同的人类线粒体疾病（包括癌症）中经常发生改变。mtDNA突变分析可能是一个宝贵的工具，分子评估组织学阴性的边缘，以及监测HNSCC患者局部复发。
Mitochondrial DNA (mtDNA) mutations were reported in primary head and neck squamous cell carcinoma (HNSCC) patients. However, very little information is available on the mtDNA mutation pattern in the histologically negative surgical margins and tumors of HNSCC patients who experienced tumor recurrence. The present study aimed at understanding the nature and timing of mtDNA mutation in histologically negative margins, and tumors in HNSCC patients who developed local recurrence during the follow ups. The entire 16.5-kb mitochondrial genome was sequenced in matched normal lymphocytes, histologically normal margins, and tumors of 50 recurrent HNSCC patients. The mtDNA mutations were then compared with clinical parameters. Forty-eight percent (24 of 50) patients harbored at least one somatic mtDNA mutation in the tumor, and a total of 37 somatic mtDNA mutations were detected. The mtDNA mutations were mostly heteroplasmic in nature and nucleotide transitions (A↔G; T↔C). Forty-six percent of the mutations (17 of 37) were detected in the tumors and were also detectable in the corresponding histologically normal margin of the patients. The mtDNA mutations involved both coding and noncoding regions of the mtDNA. Majority (9 of 17, 53%) of the noncoding mutations involved tRNAs. Seventy-five percent (15 of 20) of the coding mtDNA mutations were nonsynonymous in nature and mainly affected cytochrome c oxidase (Complex IV), frequently altered in different human mitochondrial diseases including cancer. Analysis of mtDNA mutation could be an invaluable tool for molecular assessment of histologically negative margins and as well for monitoring HNSCC patients with locoregional recurrences.