High frequency of common deletion (4981 bp) in mitochondrial DNA in nasopharyngeal carcinoma and its correlation with patient age and clinical stages.
Mitochondrial DNA (mtDNA) has a high mutation rate due at least in part to a lack of protective histones and an inefficient DNA repair system. The most frequently change in mtDNA is the so-called Common Deletion (CD), which accumulates in patients with heteroplasmic mtDNA mutations and in normal individuals during aging. In this study, wild type mtDNA (WT-mtDNA) and mitochondrial DNA with CD (CD-mtDNA) were quantitatively analyzed in different nasopharynx lesions. A novel type of CD-mtDNA (4981 bp) was detected significantly higher in nasopharyngeal carcinoma (NPC) (93%, 54/58) than in nasopharyngitis (60%, 28/47) and the paired white blood cells (WBC) (26%, 8/31). The ratio of CD-mtDNA to WT-mtDNA in NPC (0.000625, median) was ten times that in nasopharyngitis (0.000064, median) (P=0.003), and was significantly higher than that in paired WBC (0.000000, median) (P=0.000). The CD/WT-mtDNA ratio was 0.000564 (quartile range, 0.000184-0.000919) in late stage NPC, which was nearly three times the ratio in early stage NPC (0.000164, quartile range, 0.000042-0.000353) (P=0.015, Mann-Whitney Test). In NPC patients with ages <48yrs (mean age), the ratio of CD-mtDNA to WT-mtDNA was 0.000625, which was nearly ten times that in NPC patients with ages<48yrs (0.000064) (P=0.005, Mann-Whitney Test). This is the first quantitative study of CD-mtDNA mutations in NPC, which provides evidences that CD-mtDNA mutation might be involved in the development and progression of NPC.
Cancer Center, Sun Yat-Sen University, Guangzhou, P.R. China.
Jian-Yong
JY
Shao
Yu-Hong
YH
Li
Hong-Yi
HY
Gao
Hai-Qiang
HQ
Mai
Yu
Y
Zhang
Xiang
X
Guo
Yi-Xin
YX
Zeng
D000328:Adult; D000367:Age Factors; D000368:Aged; D020029:Base Pairing; D001483:Base Sequence; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D009304:Nasopharyngitis / Q000175:diagnosis / Q000235:genetics; D010614:Pharynx / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial; D005819:Genetic Markers