-Original-

Mitochondrial DNA Alterations in Colorectal Cancer Cell Lines

Naoto Chihara^1-3, Taku Amo¹, Akira Tokunaga^2,3, Ryo Yuzuriha¹, Alexander M. Wolf¹, Sadamitsu Asoh¹, Hideyuki Suzuki^2,3, Eiji Uchida² and Shigeo Ohta¹

¹Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School
²Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School
³Institute of Gastroenterology, Nippon Medical School Musashi Kosugi Hospital

Somatic mutations of mitochondrial DNA (mtDNA) have been reported in different types of cancers and are suggested to play roles in metastasis, cancer development and response to anticancer agents. To predict potential roles of mtDNA alterations in colorectal cancer, we determined the entire mtDNA sequence of eleven human-derived colorectal cancer cell lines and compared with the revised Cambridge Reference Sequence to identify nucleotide alterations. Four homoplasmic and six heteroplasmic alterations were found to be novel. Among them, homoplasmic G6709A (MT-CO1) and G14804A (MT-CYB) alterations cause amino acid changes in the highly conserved residues. Heteroplasmic G1576A (MT-RNR1) and G2975A (MT-RNR2) alterations are expected to make the stem structure of mitochondrial ribosomal RNAs unstable. These nucleotide alterations are candidates that could play important roles in cancer.

J Nippon Med Sch 2011; 78: 13-21

Keywords
mtDNA, colorectal cancer, mitochondria, nucleotide sequence

Correspondence to
Shigeo Ohta, Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan
ohta@nms.ac.jp

Received, August 13, 2010
Accepted, October 7, 2010