Tumor‐specific changes in mtDNA content in human cancer

Abstract

Mitochondrial DNA (mtDNA) alterations are associated with various cancer types, suggesting that the mitochondrial genome may be a critical contributing factor in carcinogenesis. mtDNA alterations have been suggested as a potentially sensitive and specific biomarker for several cancer types. We examined mtDNA content in 25 pairs of normal and tumor breast tissue samples, 37 papillary thyroid carcinoma (PTC), 21 benign thyroid neoplasms and in 20 paired normal and PTC samples. Our results showed that mtDNA content was reduced in 80% of the breast tumors relative to their corresponding normal. mtDNA was increased in papillary thyroid carcinomas, however, when compared to the corresponding normal DNA taken from the same individual. Also, mtDNA content was increased in none-paired PTC samples compared to the normal controls. Our findings indicate that changes in mtDNA content during carcinogenesis may be regulated in a tumor specific manner. Additionally, changes in mtDNA levels did not correlate with tumor grade and metastasis, suggesting that these alterations may occur in the early stages of tumorigenesis. Our findings suggest that mtDNA content can be used as a molecular diagnostic tool to help identify genetic abnormalities in human tumors. ' 2005 Wiley-Liss, Inc.

Correlation of telomere length shortening with promoter methylation profile of p16/Rb and p53/p21 pathways in breast cancer

“…32 However, our results showed a significant correlation between telomere length shortening and distant metastasis (Po0.05) (Figure 3). Although we could not find any significant correlation between telomere length and age (Z50 vs o50) in cancer tissue (Figure 5a), a significant shortened telomere length was observed in patients over the age of 50 years (Po0.05) (Figure 5b).…”

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

“…No relationship was found between the decrease and those parameters. It was likewise shown by Mambo et al (2005) that changes in mtDNA content in breast cancer did not correlate with tumour grade and metastasis, suggesting that these alterations may occur in the early stages of tumorigenesis.…”

“…Quantitative aberrations of mtDNA have been observed in various sample types from patients with cancers (Mambo et al 2005). While increased mtDNA content has been found in prostate (Mizumachi et al 2008a), head and neck (Kim et al 2004), endometrial adenocarcinoma (Wang et al 2005), etc., reduced mtDNA content in renal (Meierhofer et al 2004) and liver cancers (Yin et al 2004) has been reported.…”

Mitochondrial DNA mutations in human cancer

“…Differences in the ultra structure of mitochondria (Hoberman, 1975;Springer, 1980), and depletion cellular mitochondrial numbers have been reported in liver carcinogenesis (Cuezva et al, 2002). Also, as discussed above, differences in content and composition of all oxidative phosphorylation complexes (Irwin et al, 1978;Cuezva et al, 2002;Simonnet et al, 2002) respiratory chain activity (Boitier et al, 1995;Rossignol et al, 2004) expression of oxidative phosphorylation genes (Weber et al, 2002) and levels of mitochondrial DNA (Simonnet et al, 2002;Meierhofer et al, 2004;Mambo et al, 2005) were reported relative to normal controls.…”