Mitochondrial D-loop mutation is a common event in colorectal cancers with p53 mutations.
OBJECTIVE
p53 is the most frequently mutated gene in colorectal cancer. In mitochondria, p53 protein is involved in regulation of transcription/replication and maintenance of genomic stability. Our aim was to examine the relationship between p53, D-loop mutation, and mitochondrial DNA content in colorectal cancer (CRC).


METHODS
A total of 194 patients with sporadic CRC without microsatellite instability who underwent surgery in Taipei Veterans General Hospital from January 1999 to December 2000 were included. The mitochondrial DNA content and D-loop mutation were quantified using real-time PCR and sequencing.


RESULTS
D-loop mutation occurred at significantly higher frequency in tumors with p53 mutation (34/88; 38.6%) than in tumors without p53 mutation (23/106; 21.7%). The frequency of the decreased mtDNA content was significantly associated with TNM stage (p = 0.009) and p53 mutation (p = 0.036). The 5-year DFS rate was 39% in patients exhibiting tumors with decreased mtDNA content, and was significantly poorer in these patients than in those exhibiting tumors with normal level of mtDNA content (61%, p = 0.01). The presence of D-loop mutations had no effect on 5-year DFS rate. In multivariate survival analysis, TNM stage, and p53 mutation, but not decreased mtDNA content and D-loop instability, had significant impacts on prognosis.


CONCLUSIONS
Change of mitochondrial DNA is a common event in colorectal cancer with p53 mutation, but is not associated with prognosis of CRC patients.
Chang
Shih-Ching
SC
Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan.
Lin
Pei-Ching
PC
Yang
Shung-Haur
SH
Wang
Huann-Sheng
HS
Liang
Wen-Yih
WY
Lin
Jen-Kou
JK
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009690:Nucleic Acid Conformation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004272:DNA, Mitochondrial; D016159:Tumor Suppressor Protein p53