کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1967005 | 1645464 | 2010 | 5 صفحه PDF | دانلود رایگان |
BackgroundSomatic mutations and germline variations in mitochondrial DNA (mtDNA) have been widely detected in a range of human malignancies including Ewing's sarcoma (EWS). However, it still remains unknown whether quantitative alterations in mtDNA level occur during the initiation and/or progression of EWS.MethodsTo test this possibility, we determined mtDNA copy number from 17 cases of EWS tumor tissues and 5 normal bone tissue samples using a quantitative real-time PCR assay.ResultsOur results showed that the average mtDNA content was significantly reduced in cancerous specimens as compared to that in normal bone controls. mtDNA copy number was statistically associated with tumor metastasis. There was an over 2-fold decrease in tumors with metastasis than in low-grade ones without metastasis. In addition, change in mtDNA content was related to somatic mutations in the D-loop control region. Tumors harboring D-loop mutations, at the polycytidine stretch between nucleotide positions 303 and 309 or close to the replication origin sites of the heavy strand, exhibited significantly lowered mtDNA levels in comparison with those without D-loop alterations.ConclusionsThe mtDNA content reduction may be an important genetic event in the carcinogenesis of EWS. This study provides evidence that somatic D-loop mutation is likely one of the key factors contributing to quantitative changes of mtDNA in EWS.
Journal: Clinica Chimica Acta - Volume 411, Issues 9–10, 2 May 2010, Pages 679–683