title: Mutational hotspots in the mitochondrial genome of lung cancer.
abstract: We determined the somatic mutations in the mitochondrial genomes of 70 lung cancer patients by pair-wise comparative analyses of the normal- and tumor-genome sequences acquired using Affymetrix Mitochondrial Resequencing Array 2.0. The overall mutation rates in lung cancers were Approximately 100 fold higher than those in normal cells, with significant statistical correlation with smoking (p=0.00088). Total of 532 somatic mutations were evenly distributed in 499 positions with very low overall frequency (1.07/bp), but the non-synonymous mutations causing amino acid substitution occurred more frequently (1.83/bp), particularly at two positions, 8701 and 10398 (10.5/bp) that code for ATPase6 and NADH dehydrogenase 3, respectively. Despite the randomness or even distribution of the mutations, these two mutations occurred together in 86% of the cases. The linkage between the two most frequent mutations suggests that they were selected together, possibly due to their cooperative role during cancer development. Indeed, the mutation at 10398 was shown by Canter, Pezzotti, and their colleagues in 2009, as a risk factor for breast cancer. In this study, we identified two potential biomarkers that might be functionally linked together during the development of cancer.
authors.affiliation: Cancer Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, Korea.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Choi
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho Y
authors.initials: HY
authors.lastname: Kang
authors.forename: Jinseon
authors.initials: J
authors.lastname: Lee
authors.forename: Jong H
authors.initials: JH
authors.lastname: Bhak
authors.forename: Insuk
authors.initials: I
authors.lastname: Sohn
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Choi
authors.forename: Hong Kwan
authors.initials: HK
authors.lastname: Kim
authors.forename: Jungho
authors.initials: J
authors.lastname: Han
authors.forename: Nam
authors.initials: N
authors.lastname: Huh
authors.forename: Gyusang
authors.initials: G
authors.lastname: Lee
authors.forename: Byung C
authors.initials: BC
authors.lastname: Kim
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D016296:Mutagenesis; D011110:Polymorphism, Genetic; D056910:Republic of Korea; D012907:Smoking / Q000235:genetics
chemical_list: C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human