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  1. NTU Scholars
  2. 醫學院
  3. 醫學檢驗暨生物技術學系
Please use this identifier to cite or link to this item: https://scholars.lib.ntu.edu.tw/handle/123456789/507689
Title: Mitochondrial genomic instability in colorectal cancer: No correlation to nuclear microsatellite instability and allelic deletion of hMSH2, hMLH1, and p53 Genes, but prediction of better survival for dukes' stage C disease
Authors: Tsai M.-H.
WOEI-HORNG FANG 
Lin S.-W.
Yen S.-J.
Chou S.-J.
Yang Y.-C.
Issue Date: 2009
Journal Volume: 16
Journal Issue: 10
Start page/Pages: 2918-2925
Source: Annals of Surgical Oncology
Abstract: 
Purpose. Malfunction of mismatch repair (MMR) system and p53 produces nuclear genomic instability and is involved in colorectal tumorigenesis. In addition to a nuclear genome, eukaryotic cells have cytoplasmic genomes that are compartmentalized in the mitochondria. The aims of this study were to detect the mitochondrial genomic instability (mtGI) in colorectal carcinomas, and to explore its relationship with nuclear genetic alterations and its prognostic meaning. Methods. Eighty-three colorectal carcinomas with corresponding normal mucosa were analyzed for mtGI, nuclear microsatellite instability (nMSI), and loss of heterozygosity (LOH) of hMSH2, hMLH1, and p53 genes. Mitochondrial and nuclear alterations were examined for mutual correlation and for associations with clinicopathological features and clinical outcomes. Results. Out of 83 cases, mtGI was identified in 23 carcinomas (27.7%), whereas nMSI was detected in 11 (13.3%). Of the 23 cases with mtGI, only two showed nMSI simultaneously. The frequencies of LOH of hMSH2, hMLH1, and p53 were 16.1%, 11.6%, and 65.3%, respectively. There was no significant association between mtGI and these allelic losses. Notably, Dukes' C patients with mtGI had better disease-free and overall survival than those lacking this feature (p = 0.0516 and 0.0313, respectively). Conclusions. Mitochondrial genomic instability occurs with a high frequency in colorectal carcinomas but is independent of nMSI and allelic deletion of hMSH2, hMLH1, and p53 genes. The results suggest that, instead of nuclear MMR system, there might be different mechanisms involving mitochondrial genomic integrity, and mtGI confers a better prognosis in Dukes' C colorectal cancer. ? 2009 Society of Surgical Oncology.
URI: https://scholars.lib.ntu.edu.tw/handle/123456789/507689
ISSN: 1068-9265
DOI: 10.1245/s10434-009-0581-7
metadata.dc.subject.other: protein MLH1; protein MSH2; protein p53; mitochondrial DNA; MLH1 protein, human; MSH2 protein, human; nuclear protein; protein MSH2; protein p53; signal transducing adaptor protein; TP53 protein, human; tumor marker; adult; aged; allele; article; cancer survival; colorectal carcinoma; controlled study; disease association; disease free survival; disease severity; female; gene deletion; gene frequency; genomic instability; heterozygosity loss; human; human tissue; major clinical study; male; microsatellite instability; mitochondrial genome; overall survival; prognosis; cancer staging; cell nucleus; colorectal tumor; follow up; gene deletion; genetics; middle aged; mitochondrion; pathology; survival rate; Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Cell Nucleus; Colorectal Neoplasms; DNA, Mitochondrial; Female; Follow-Up Studies; Humans; Loss of Heterozygosity; Male; Microsatellite Instability; Middle Aged; Mitochondria; MutS Homolog 2 Protein; Neoplasm Staging; Nuclear Proteins; Prognosis; Sequence Deletion; Survival Rate; Tumor Markers, Biological; Tumor Suppressor Protein p53
[SDGs]SDG3
Appears in Collections:醫學檢驗暨生物技術學系

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