Abstract
Somatic mutations in mtDNA have recently been identified in colorectal tumours. Studies of oncocytic tumours have led to hypotheses which propose that defects in oxidative phosphorylation may result in a compensatory increase in mitochondrial replication and/or gene expression. Mutational analysis of mtDNA in thyroid neoplasia, which is characterised by increased numbers of mitochondria and is also one of the most common sites of oncocytic tumours. has been limited to date. Using the recently developed technique of two-dimensional gene scanning, we have successfully examined 21 cases of thyroid tumours, six cases of non-neoplastic thyroid pathology, 30 population controls, nine foetal thyroid tissues and nine foetal tissues of non-thyroid origin, either kidney or liver. We have identified three different somatic mutations (23%) in papillary thyroid carcinomas. In addition, we have found significant differential distributions of mtDNA sequence variants between thyroid carcinomas and controls. Interestingly, these variants appear to be more frequent in the genes which encode complex I of the mitochondrial electron transport chain compared to normal population controls. These findings suggest first, that somatic mtDNA mutations may be involved in thyroid tumorigenesis and second, that the accumulation of certain non-somatic variants may be related to tumour progression in the thyroid.
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References
Alonso A, Martin P, Albarran C, Aquilera B, Garcia O, Guzman A, Oliva H and Sancho M . 1997 Electrophoresis 18: 682–685
Ausubel F, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA and Struhl K ed . 1994–1998 Current Protocols in Molecular Biology John Wiley and Sons, Inc, USA
Bianchi MS, Bianchi NO and Bailliet G . 1995 Cytogenet Cell Genet 71: 99–103
Burgart LJ, Zheng J, Shu Q, Strickler JG and Shibata D . 1995 Am J Pathol 147: 1105–1111
Cavalli LR and Liang BC . 1998 Mutat Res 398: 19–26
Dhanda RK, van Orsouw NJ, Sigalas I, Eng C and Vijg J . 1998 Biotechniques 25: 664–668 670 672–675
Ebner D, Rodel G, Pavenstaedt I and Haferkamp O . 1991 Virchows Arch B Cell Pathol Incl Mol Pathol 60: 139–144
Green DR and Reed JC . 1998 Science 281: 1309–1312
Horton TM, Petros JA, Heddi A, Shoffner J, Kaufman AE, Graham Jr SD, Gramlich T and Wallace DC . 1996 Genes Chrom Cancer 15: 95–101
Johnson D, Tallini G, Silna D, Liang M and Wong L . 1996 Am J Pathol 149: 1786
Muller-Hocker J, Jacob U and Seibel P . 1998 Ultrastruct Pathol 22: 91–100
Oberley LW and Oberley TD . 1998 Mol Cell Biochem 84: 147–153
Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, Trush MA, Kinzler KW and Vogelstein B . 1998 Nat Genet 20: 291–293
Sigel S and Castellan N . 1998 Nonparametric Statistics for the Behavioural Sciences, Second edn McGraw-Hill New York
Simon DK and Johns DR . 1999 Annu Rev Med 50: 111–127
Stefaneanu L and Tasca C . 1979 Endocrinologie 17: 233–239
Tallini G, Ladanyi M, Rosai J and Jhanwar SC . 1994 Cytogenet Cell Genet 66: 253–259
van Orsouw NJ, Zhang X, Wei JY, Johns DR and Vijg J . 1998 Genomics 52: 27–36
Wallace DC . 1992 Science 256: 628–632
Wallace DC . 1994 Proc Natl Acad Sci USA 91: 8739–8746
Wallace DC . 1999 Science 283: 1482–1488
Welter C, Kovacs G, Seitz G and Blin N . 1989 Genes Chromosomes Cancer 1: 79–82
Acknowledgements
JJ Yeh thanks James Becker for his continued support. The authors wish to acknowledge Jennifer B Kum, Sean McGrath and Wendy M Smith for technical advice. Partially funded by P30CA16058 from the National Cancer Institute (Ohio State University Comprehensive Cancer Center), a Boston University School of Medicine Surgical Research Fellowship (to JJ Yeh), and generous gifts from the Brown and Abrams families (to C Eng). PLM Dahia is a recipient of a postdoctoral fellowship from the Susan G Komen Breast Cancer Research Foundation (to C Eng).
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Yeh, J., Lunetta, K., van Orsouw, N. et al. Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours. Oncogene 19, 2060–2066 (2000). https://doi.org/10.1038/sj.onc.1203537
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DOI: https://doi.org/10.1038/sj.onc.1203537
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