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Mutagenesis Advance Access published online on February 4, 2008
Mutagenesis, doi:10.1093/mutage/gen002
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© The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Tandem duplication/triplication correlated with poly-cytosine stretch variation in human mitochondrial DNA D-loop region

Wen-Yi Hung1, Jin-Ching Lin2, Liang-Ming Lee3, Chew-Wun Wu4, Ling-Ming Tseng4, Pen-Hui Yin5, Chin-Wen Chi1,5 and Hsin-Chen Lee1,*

1Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China 2Department of Radiation Oncology, Taichung Veterans General Hospital, Taiwan, Republic of China 3Department of Urology, Taipei Medical University—Affiliated Taipei Municipal Wan-Fang Hospital, Taiwan, Republic of China 4Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, Republic of China 5Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan, Republic of China

Somatic mutations in the mitochondrial DNA (mtDNA) displacement loop (D-loop) region have been frequently detected in various human cancers. In a previous study, we identified a polyplasmic 260-bp tandem duplication and triplication mutation in the mtDNA D-loop of one gastric cancer. In the present study, we adopted a more sensitive back-to-back polymerase chain reaction method to screen for this 260-bp tandem duplication/triplication in 197 cancers and their adjacent non-cancerous tissues. Nine samples of primary cancer (4.6%) were found to harbor the tandem duplication/triplication and these were made up of four out of 31 (12.9%) gastric cancers, two out of 45 (4.4%) breast cancers, two out of 56 (3.6%) hepatocellular cancers and one out of 32 (3.1%) colon cancers, but no tandem duplication/triplication was present in any of 33 lung cancers. We also found an expanded and polyplasmic poly-cytosine (poly-C) stretch around nucleotide position (np) 568 in eight of the 197 (4.1%) cancer patients. All the eight cancer samples carried the 260-bp tandem duplication/triplication. In addition, we detected the np 568 poly-C length variations in 11 of 234 (4.7%) peripheral blood samples of non-cancer population and the 260-bp tandem duplication in nine of the 11 cases with the np 568 poly-C length variations. These observations suggest that the occurrence of the tandem duplication/triplication in mtDNA D-loop is not specific for cancer tissues, but highly associated with the poly-C length variations around np 568.

* To whom correspondence should be addressed. Tel: +886 2 28267327; Fax: +886 2 28264372; Email: hclee2{at}ym.edu.tw

Received on August 23, 2007; revised on December 19, 2007; accepted on December 30, 2007.


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