title: High-frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values.
abstract: Most studies of mitochondrial DNA (mtDNA) mutations in colorectal cancer have used case-control and case-database comparisons without searching their clinical relevance. This study was to investigate colorectal cancer tissue-specific mtDNA mutations from 54 matched colorectal cancer and adjacent normal tissues and then to evaluate their clinical values. This study focused on analyzing control region including mtDNA minisatellites and coding regions. Cancer tissue-specific mtDNA mutations were found in over half of the patients (59%). The patterns of mtDNA mutations were substitution only (13%), mtDNA minisatellite instability (mtMSI) (20%) and both mutations combined (26%). mtMSI in colorectal cancer was mainly occurred in the 303 polyC (35%) and 16184 poly C (19%) minisatellite. mtDNA copy number and hydrogen peroxide level were significantly increased in colorectal cancer tissue. The amount of mtDNA large deletions was significantly decreased in colorectal cancer tissue compared with those from matched normal mucosa (p = 0.03). The activity of the mitochondrial respiratory chain enzyme complexes I, II and III in colorectal cancer tissues was impaired. mtDNA haplogroup B4 might be closely associated with colorectal cancer risk. The patient group harboring cancer tissue-specific mtDNA mutations showed larger tumor sizes (p = 0.005) and more advanced TNM stages (p = 0.002). Thus, mtDNA mutations in colorectal cancer might be implicated in risk factors that induce poor outcomes and tumorigenesis.
authors: Department of Surgery, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, South Korea.
authors: Sang Woo
authors: SW
authors: Lim
authors: Hye Ran
authors: HR
authors: Kim
authors: Hwan Young
authors: HY
authors: Kim
authors: Jung Wook
authors: JW
authors: Huh
authors: Young Jin
authors: YJ
authors: Kim
authors: Jong Hee
authors: JH
authors: Shin
authors: Soon Pal
authors: SP
authors: Suh
authors: Dong Wook
authors: DW
authors: Ryang
authors: Hyeong Rok
authors: HR
authors: Kim
authors: Myung Geun
authors: MG
authors: Shin
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D054629:Genome, Mitochondrial; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D018598:Minisatellite Repeats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species