Relationship between mitochondrial DNA mutations and clinical characteristics in human lung cancer Xiongjie Jin a,b,1 , Jianjun Zhang a,1 , Yanning Gao a , Keyue Ding b,c , Naishu Wang d , David Zhou d , Jin Jen e , Shujun Cheng a, * a Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, PO Box 2258, Beijing 100021, PR China b Chinese National Human Genome Center, Beijing, 3-707 North Yongchang Road, BDA, Beijing 100176, PR China c National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, 5 Dongdan Santiao, Beijing 100005, PR China d Alfa Scientific Designs Inc., 12330 Stowe Drive Poway, CA 92064, USA e Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, Building 41, Room D702, 41 Library Drive, Bethesda, MD 20892, USA Received 6 August 2006; received in revised form 12 May 2007; accepted 26 June 2007 Available online 4 July 2007 Abstract Mitochondrial DNA (mtDNA) is known for its high frequencies of polymorphisms and mutations, some of which are related to var- ious diseases, including cancers. However, roles of mutations and polymorphisms in some diseases are among heated debate, especially for cancer. To investigate the possible role of mtDNA mutations in lung cancer, we sequenced complete mtDNA of lung cancer tissues, corresponding normal (i.e., non-cancerous) lung tissues, and peripheral blood samples from 55 lung cancer patients and examined the relationship between mtDNA mutations or polymorphisms and clinical parameters. We identified 56 mutations in 33 (60%) of the 55 patients, including 48 point mutations, four single-nucleotide insertions, and four single-nucleotide deletions. Nineteen of these muta- tions resulted in amino acid substitution. These missense mtDNA mutations were distributed in 9 of 13 mitochondrial DNA coding genes. Three hundred eighty eight polymorphisms were identified among the 55 patients. Seventy-three polymorphisms resulted in amino acid substitution. There was no association of incidence of specific mtDNA mutation or polymorphism with patients’ gender, age at diag- nosis, smoking history, tumor type or tumor stage (P > 0.05). This study revealed a variety of mtDNA mutations and mtDNA polymor- phisms in human lung cancer, some of which might be involved in human lung carcinogenesis. Ó 2007 Elsevier B.V. and Mitochondria Research Society. All rights reserved. Keywords: Mitochondrial DNA; Mutation; Lung cancer 1. Introduction Human mitochondrial DNA (mtDNA) is a 16,569 base- pair (bp) circular double-stranded DNA molecule that encodes 13 polypeptides involved in oxidative phosphory- lation, 22 transfer RNAs (tRNAs), and two ribosomal RNAs (rRNAs). Most cells contain 10 3 –10 4 copies of mtDNA and the mutation rate of mtDNA is much higher than that of nuclear DNA (Wallace, 1994). The high copy number and the high mutation rate are two important fea- tures that distinguish mtDNA from nuclear DNA. Mitochondrial dysfunction is increasingly recognized as an important cause of human pathology. There are now more than 50 disease-causing mtDNA mutations and hun- dreds of mtDNA rearrangement known (Simon and Johns, 1999; Wallace, 1999; Larsson and Luft, 1999). Over the past decade, many somatic mtDNA mutations have been identified in various tumor tissues and cell lines, including 1567-7249/$ - see front matter Ó 2007 Elsevier B.V. and Mitochondria Research Society. All rights reserved. doi:10.1016/j.mito.2007.06.003 * Corresponding author. Tel.: +86 10 6778 2323; fax: +86 10 6776 7548. E-mail address: chengshj@263.net.cn (S. Cheng). 1 These authors contributed equally to this work. www.elsevier.com/locate/mito Mitochondrion 7 (2007) 347–353