Carcinogenesis Advance Access published online on September 16, 2004
Carcinogenesis, doi:10.1093/carcin/bgh282
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Ellis Fischel Cancer Center and Department of Surgery, University of Missouri, Columbia, MO 65212
* To whom correspondence should be addressed. E-mail: sautere{at}health.missouri.edu.
Background: Unlike nuclear (n)DNA, of which there is one paired copy per cell, there are many copies of mitochondrial (mt)DNA per cell, making PCR amplification of mtDNA easier in samples of limited cellularity. The aims of this study were to 1) determine the mutation patterns of breast cancers through a comprehensive screen of mtDNA mutations, and 2) assess if mutations in the cancers are also detectable in breast nipple aspirate fluid (NAF), a physiologic fluid which contains shed ductal epithelial cells. Materials and methods: 15 breast cancers, matched benign tissues and NAF were collected. 9 overlapping primer sets were used to sequence the entire mitochondrial genome from tissue samples. For NAF samples, we focused on the 19 np where mutations were found in a 3701bp region (np15331 to 2463) which includes the D-loop, a mtDNA mutation hot spot. Results: 14/15 (93%) cancer samples had 1 Supported in part by Department of Defense grant DAMD17-01-1-0426
Revised August 9, 2004
Accepted September 5, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid1
Abstract 
1 somatic mtDNA mutation for a total of 45 at 35 nucleotide positions (9 np previously reported, 26 new). 9/15 tumors had 2 mutations. The D-loop contained 17/45 (38%) and non D-loop (coding) regions contained 28 (62%) mutations. Of the 28 mutations in coding loci, 11 led to an amino acid change. The frequency of mtDNA mutations was higher in the D-loop region (1.5% vs 0.18% of loci). 155 polymorphisms were identified (98 previously reported, 57 new). 16/45 (36%) mutations were located at polymorphism sites. 4/19 mtDNA mutations in 10 cancers located between np15331 and 2463 were found in matched NAF (2/11 mutations in the D-loop and 2/8 in non D-loop regions). No mutations were found in 5 matched NAF samples from women whose cancers lacked a mutation in the same region. Conclusion: mtDNA mutations in breast cancer occur both within and outside of the D-loop, though the mutation rate in the D-loop is over 7 fold higher than in coding areas. We identified 26 new mutation loci (25 in regions sequenced by others, one in an area not). The high frequency of mtDNA mutations at polymorphic loci requires further investigation. mtDNA mutations in NAF may prove useful to aid in early breast cancer detection. Specific mtDNA mutations can be detected in a subset of NAF samples from women with breast cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Ye, Y.-T. Gao, W. Wen, J. P. Breyer, X. O. Shu, J. R. Smith, W. Zheng, and Q. Cai Association of Mitochondrial DNA Displacement Loop (CA)n Dinucleotide Repeat Polymorphism with Breast Cancer Risk and Survival among Chinese Women Cancer Epidemiol. Biomarkers Prev., August 1, 2008; 17(8): 2117 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Mannello and G. A.M. Tonti Benign Breast Diseases: Classification, Diagnosis, and Management Oncologist, November 1, 2006; 11(10): 1132 - 1134. [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Parr, G. D. Dakubo, K. A. Crandall, J. Maki, B. Reguly, A. Aguirre, R. Wittock, K. Robinson, J. S. Alexander, M. A. Birch-Machin, et al. Somatic Mitochondrial DNA Mutations in Prostate Cancer and Normal Appearing Adjacent Glands in Comparison to Age-Matched Prostate Samples without Malignant Histology J. Mol. Diagn., July 1, 2006; 8(3): 312 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Sartippour, L. Zhang, M. Lu, H.-J. Wang, and M. N. Brooks Nipple Fluid Basic Fibroblast Growth Factor in Patients with Breast Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2995 - 2998. [Abstract] [Full Text] [PDF]
|
|