Mitochondrial DNA somatic mutations are frequent in nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China, and is highly sensitive to radiotherapy. The control region (D-loop) of mtDNA is a polymorphic region in which point mutations occur frequently. In this study, point mutation and common deletion (CD) mutations were investigated in 23 samples of NPC tumor tissue and in the radiation-treated NPC cell line CNE2. Polymorphisms at 72 (7.28%, 72/988) nucleotide positions in D-loop region and 6 (0.75%, 6/795) nucleotide positions in part of the functional gene encoding regions were detected in all NPC patients. Of the detected polymorphisms, 8 are novel. These variants are nonencoding transitions, including np292T-->C , np517G-del, np16038A-->G, np513G-del, np16242C-->A, np513G-del, np16242C-->A and np15787T-->C transition. A total of 39 point mutations in the D-loop region of mtDNA were detected in 43.5% (10/23) of the NPC patients. Three point mutations in the functional gene encoding regions of mtDNA were detected in only 8.7% (2/23) of NPC patients. The effect of he mutation at np709G-->A in the 12sRNA gene is unclear, and the A-->G substitution at np15769 in the cytochrome B gene is a synonymous mutation. The C-->T substitution at np15970 in the T Psi C loop of the tRNA(pro) gene could alter the position of the proline residue. After irradiation, the survival fraction of CNE2 cells decreased as X-ray dose increased. Moreover, X-ray radiation could induce apoptosis and the CD mutation in a time- and dose-dependent manner, but did not induce mtDNA point mutations. A positive correlation between the apoptosis index and the ratio of CD/WT mtDNA was observed in irradiated CNE2 cells. Our results suggest that CD mutation induced by irradiation is one of the late events after apoptosis of the cancer cells, and the mtDNA CD mutation may associated with the susceptibility of NPC cells to IR-induced apoptosis.
Pang
Ling-Juan
LJ
Department of Pathology, Sun Yat-Sen University, Guangzhou, P.R. China.
Shao
Jian-Yong
JY
Liang
Xiao-Man
XM
Xia
Yun-Fei
YF
Zeng
Yi-Xin
YX
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000528:radiation effects; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D009367:Neoplasm Staging; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D013997:Time Factors
D004272:DNA, Mitochondrial