| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Institute of Molecular Pathology and Immunology,*the University of Porto, Porto, Portugal; the Department of Pathology,Medical Faculty of Porto, Porto, Portugal; the Department of Pathology,Hospital São João, Porto, Portugal; and the Department of Pathology,Hospital Clínico Universitario, Santiago de Compostela, Spain
In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the mtDNA in 79 benign and malignant tumors (43 Hürthle and 36 non-Hürthle cell neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was evaluated by semiquantitative polymerase chain reaction. Somatic point mutations and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations, mostly transitions, in 34 tumors and 253 sequence variants in 59 patients. Follicular and papillary carcinomas carried a significantly higher prevalence of nonsilent point mutations of complex I genes than adenomas. We also detected a significantly higher prevalence of complex I and complex IV sequence variants in the normal parenchyma adjacent to the malignant tumors. Every Hürthle cell tumor displayed a relatively high percentage (up to 16%) of mtDNA CD independently of the lesion’s histotype. The percentage of deleted mtDNA molecules was significantly higher in tumors with D-loop mutations than in mtDNA stable tumors. Sequence variants of the ATPase 6 gene, one of the complex V genes thought to play a role in mtDNA maintenance and integrity in yeast, were significantly more prevalent in patients with Hürthle cell tumors than in patients with non-Hürthle cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of complex I and complex IV genes seem to be involved in thyroid tumorigenesis. Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of mtDNA CD, the hallmark of Hürthle cell tumors.
This article has been cited by other articles:
 |
|
 |
|
  J. A. Mayr, D. Meierhofer, F. Zimmermann, R. Feichtinger, C. Kogler, M. Ratschek, N. Schmeller, W. Sperl, and B. Kofler Loss of Complex I due to Mitochondrial DNA Mutations in Renal Oncocytoma Clin. Cancer Res., April 15, 2008; 14(8): 2270 - 2275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dasgupta, M. O. Hoque, S. Upadhyay, and D. Sidransky Mitochondrial Cytochrome B Gene Mutation Promotes Tumor Growth in Bladder Cancer Cancer Res., February 1, 2008; 68(3): 700 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wang, W. R. Bamlet, M. de Andrade, L. A. Boardman, J. M. Cunningham, S. N. Thibodeau, and G. M. Petersen Mitochondrial Genetic Polymorphisms and Pancreatic Cancer Risk Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1455 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gasparre, A. M. Porcelli, E. Bonora, L. F. Pennisi, M. Toller, L. Iommarini, A. Ghelli, M. Moretti, C. M. Betts, G. N. Martinelli, et al. Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors PNAS, May 22, 2007; 104(21): 9001 - 9006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bonora, A. M. Porcelli, G. Gasparre, A. Biondi, A. Ghelli, V. Carelli, A. Baracca, G. Tallini, A. Martinuzzi, G. Lenaz, et al. Defective Oxidative Phosphorylation in Thyroid Oncocytic Carcinoma Is Associated with Pathogenic Mitochondrial DNA Mutations Affecting Complexes I and III. Cancer Res., June 15, 2006; 66(12): 6087 - 6096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shidara, K. Yamagata, T. Kanamori, K. Nakano, J. Q. Kwong, G. Manfredi, H. Oda, and S. Ohta Positive Contribution of Pathogenic Mutations in the Mitochondrial Genome to the Promotion of Cancer by Prevention from Apoptosis Cancer Res., March 1, 2005; 65(5): 1655 - 1663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sobrinho-Simoes, V. Maximo, I. V. de Castro, E. Fonseca, P. Soares, G. Garcia-Rostan, and M. C. de Oliveira Hurthle (Oncocytic) Cell Tumors of Thyroid: Etiopathogenesis, Diagnosis and Clinical Significance International Journal of Surgical Pathology, January 1, 2005; 13(1): 29 - 35. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Sadetzki, R. Calderon-Margalit, B. Modan, S. Srivastava, and R. M. Tuttle Ret/PTC Activation in Benign and Malignant Thyroid Tumors Arising in a Population Exposed to Low-Dose External-Beam Irradiation in Childhood J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2281 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S L Asa My approach to oncocytic tumours of the thyroid J. Clin. Pathol., March 1, 2004; 57(3): 225 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lima, V. Maximo, P. Soares, D. Williams, T. Bogdanova, G. A. Thomas, and M. Sobrinho-Simoes Re: Lohrer,H.D., Hieber,L. and Zitzelsberger,H. (2002) Differential mutation frequency in mitochondrial DNA from thyroid tumours. Carcinogenesis, 23, 1577-1582 Carcinogenesis, June 1, 2003; 24(6): 1155 - 1155. [Full Text] [PDF]
|
|
|
|
|
|
L. Cheung, M. Messina, A. Gill, A. Clarkson, D. Learoyd, L. Delbridge, J. Wentworth, J. Philips, R. Clifton-Bligh, and B. G. Robinson Detection of the PAX8-PPAR{gamma} Fusion Oncogene in Both Follicular Thyroid Carcinomas and Adenomas J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 354 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. I. Rogounovitch, V. A. Saenko, Y. Shimizu-Yoshida, A. Yu. Abrosimov, E. F. Lushnikov, P. O. Roumiantsev, A. Ohtsuru, H. Namba, A. F. Tsyb, and S. Yamashita Large Deletions in Mitochondrial DNA in Radiation-associated Human Thyroid Tumors Cancer Res., December 1, 2002; 62(23): 7031 - 7041. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
