Relationship between mitochondrial DNA mutations and clinical characteristics in human lung cancer

Jin, Xin; Zhang, Jianjun; Gao, Yanning; Ding, Keyue; Wang, Naishu; Zhou, David; Jen, Jin; Cheng, Shujun

doi:10.1016/j.mito.2007.06.003

Cited by 42 publications

(27 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, an increasing number of diseases have been found to be associated with mutations in the mtDNA (1)(2)(3)(4)(5)(6)(7). Furthermore, a number of different cancer types have been found to be linked to such mutations, and in many cases, these mutations result in structural modifications of enzymes of the electron-transport chain (8)(9)(10)(11). A possible factor contributing to the development of the disease is an increased production of reactive oxygen species (ROS) as a result of a specific mutation (1,9,10,12).…”

mentioning

confidence: 99%

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase

Namslauer

Brzezinski

2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

An increasing number of cancer types have been found to be linked to specific mutations in the mitochondrial DNA, which result in specific structural changes of the respiratory enzyme complexes. In this study, we have investigated the effect of 2 such mutations identified in colon cancer patients, leading to the amino acid substitutions Ser458Pro and Gly125Asp in subunit I of cytochrome c oxidase (complex IV) [Greaves et al. (2006) Proc Natl Acad Sci USA 103:714 -719]. We introduced these mutations in Rhodobacter sphaeroides, which carries an oxidase that serves as a model of the mitochondrial counterpart. The lack of expression of the former variant indicates that the amino acid substitution results in severely altered overall structure of the enzyme. The latter mutation (Gly171Asp in the bacterial oxidase) resulted in a structurally intact enzyme, but with reduced activity (approximately 30%), mainly due to slowed reduction of the redox site heme a. Furthermore, even though the Gly171Asp CytcO pumps protons, an intrinsic proton leak was identified, which would lead to a decreased overall energy-conversion efficiency of the respiratory chain, and would also perturb transport processes such as protein, ion, and metabolite trafficking. Furthermore, the specific leak may act to alter the balance between the electrical and chemical components of the proton electrochemical gradient. cytochrome aa3 ͉ electrochemical ͉ electron transfer ͉ pump ͉ respiratory oxidase

show abstract

mentioning

confidence: 99%

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase

Namslauer

Brzezinski

2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Significantly, all of these mutations were present in the majority of the tumour cells and 90% of them were detectable in all of the mitochondrial DNA present in cells, strongly suggesting that all mitochondrial DNA molecules in the mitochondrion contain the same mutation. Breast cancer also exhibit somatic mitochondrial DNA mutations (Parrella et al, 2001;Radpour et al, 2009), in addition to kidney (Meierhofer et al, 2006) (Nagy et al, 2003), stomach (Hung et al, 2010;Jeong et al, 2010), prostate (Moro et al, 2009) (Parr et al, 2006) liver (Vivekanandan et al, 2010;Zhang et al, 2010), bladder (Dasgupta et al, 2008, head and neck (Allegra et al, 2006;Dasgupta et al, 2010;Mithani et al, 2007) and lung (Dai et al, 2006;Jin et al, 2007;Suzuki et al, 2003). Furthermore increased mitochondrial DNA mutation frequencies were associated with hereditary paraganglioma (Muller et al, 2005;Taschner et al, 2001) and thyroid cancers (Abu-Amero et al, 2005;Rogounovitch et al, 2004).…”

Section: Mitochondrial Dna Repair and Cancermentioning

confidence: 99%

“…Somatic mutations in mitochondrial DNA are increasingly linked to common diseases, including age-related degenerative disorders and cancers. Specifically, mitochondrial DNA mutations have been detected in colorectal (Habano et al, 1998;Polyak et al, 1998), breast (Parrella et al, 2001;Radpour et al, 2009) bladder (Copeland et al, 2002;Dasgupta et al, 2008;Wada et al, 2006), lung (Dai et al, 2006;Jin et al, 2007;Suzuki et al, 2003), head and neck cancers (Dasgupta et al, 2010) (Allegra et al, 2006;Mithani et al, 2007), amongst others. Furthermore, some evidence also exists suggesting that mutations in mitochondrial DNA can even accelerate disease progression (Ishikawa and Hayashi, 2010;Lee et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Repair

Martin¹

2011

DNA Repair - On the Pathways to Fixing DNA Damage and Errors

View full text Add to dashboard Cite

“…These mutations have been detected with relatively higher frequency by comparison between the primary cancerous, matched para-cancerous normal, and distant normal tissues from the same patients (Brandon et al, 2006;Chatterjee et al, 2006). To date, a large number of somatic mutations have been detected among various kinds of tumor tissues, such as in breast cancer (Wang et al, 2007;Alhomidi et al, 2013), gastric cancer (Hung et al, 2010), esophageal squamous cell carcinoma (Kumimoto et al, 2004), lung cancer (Jin et al, 2007;Wang and Zhao, 2011;Fang et al, 2013;Yang Ai et al, 2013), and in aging individuals (Williams et al, 2013). Our previous study also revealed elevated somatic mutation rates through the examination of thirty entire mtDNA genomes from ten Chinese patients with lung cancer (Fang et al, 2013), as well as the poly-C repeat stretch (D310) of 79 patients (Chen et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Southwest China

Yang

Shi

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Mitochondrial DNA mutations play crucial roles in the pathogenesis and progression of human malignancies. Therefore, to determine whether maternal background or mitochondrial DNA somatic mutations were essential cofactors in the lung cancer of Chinese patients as well, the complete mitochondrial DNA displacement loop of the primary cancerous, matched para-cancerous normal and distant normal tissues for 79 Chinese patients with lung cancer were analyzed in this study. Our results indicated that the higher detected frequency of haplogroups prevalent in southern East Asia (53.16%; 42/79) versus those of northern East Asia in the studied population supported the southern East Asian characteristics of the Chinese lung cancer group. Further statistical analysis revealed that the haplogroups F* and G* contributed to the susceptibility to lung cancer in Chinese patients. In addition, by comparing sequences from different tissues of the same patients, a total of eight somatic mutations from six patients were detected. Combined with the fourteen somatic mutations identified in our previous study, the somatic mutation spectrum of the 79 Chinese patients with lung cancer was 25.32% (20/79). Our results suggest that mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Yunnan, Southwest China, and that somatic mitochondrial DNA mutations in the displacement loop can serve as potential biomarkers for clinical utility.

show abstract

Relationship between mitochondrial DNA mutations and clinical characteristics in human lung cancer

Cited by 42 publications

References 37 publications

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase

Mitochondrial DNA Repair

Mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Southwest China

Contact Info

Product

Resources

About