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High‐frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values
Author(s) -
Lim Sang Woo,
Kim Hye Ran,
Kim Hwan Young,
Huh Jung Wook,
Kim Young Jin,
Shin Jong Hee,
Suh Soon Pal,
Ryang Dong Wook,
Kim Hyeong Rok,
Shin Myung Geun
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27375
Subject(s) - mitochondrial dna , colorectal cancer , biology , minisatellite , carcinogenesis , cancer , microsatellite instability , genetics , cancer research , microbiology and biotechnology , pathology , medicine , gene , allele , microsatellite
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.