Accumulation of mutations over the entire mitochondrial genome of breast cancer cells obtained by tissue microdissection
| Autor: | Alexander W. Röck, Martina Dünser, Georg Schäfer, Christof Seifarth, Liane Fendt, Harald Niederstätter, Bettina Zelger, Helmut Klocker, Walther Parson, Gabriela Huber |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Mitochondrial DNA Breast Neoplasms Biology medicine.disease_cause DNA Mitochondrial Polymerase Chain Reaction Genome 03 medical and health sciences 0302 clinical medicine Breast cancer medicine Humans Breast Phylogeny Microdissection DNA Primers 030304 developmental biology Genetics 0303 health sciences Mutation Cancer DNA Neoplasm medicine.disease Heteroplasmy 3. Good health Haplotypes Oncology 030220 oncology & carcinogenesis Genome Mitochondrial Female Breast disease |
| Zdroj: | Breast Cancer Research and Treatment. 128:327-336 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-010-1092-8 |
| Popis: | The occurrence of heteroplasmy and mixtures is technically challenging for the analysis of mitochondrial DNA. More than that, observed mutations need to be carefully interpreted in the light of the phylogeny as mitochondrial DNA is a uniparental marker reflecting human evolution. Earlier attempts to explain the role of mtDNA in cancerous tissues led to substantial confusion in medical genetics mainly due to the presentation of low sequence data quality and misinterpretation of mutations representing a particular haplogroup background rather than being cancer-specific. The focus of this study is to characterize the extent and level of mutations in breast cancer samples obtained by tissue microdissection by application of an evaluated full mtDNA genome sequencing protocol. We amplified and sequenced the complete mitochondrial genomes of microdissected breast cancer cells of 15 patients and compared the results to those obtained from paired non-cancerous breast tissue derived from the same patients. We observed differences in the heteroplasmic states of substitutions between cancerous and normal cells, one of which was affecting a position that has been previously reported in lung cancer and another one that has been identified in 16 epithelial ovarian tumors, possibly indicating functional relevance. In the coding region, we found full transitions in two cancerous mitochondrial genomes and 12 heteroplasmic substitutions as compared to the non-cancerous breast cells. We identified somatic mutations over the entire mtDNA of human breast cancer cells potentially impairing the mitochondrial OXPHOS system. |
| Databáze: | OpenAIRE |
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