Breast Cancer Research and Treatment

, Volume 128, Issue 2, pp 327–336 | Cite as

Accumulation of mutations over the entire mitochondrial genome of breast cancer cells obtained by tissue microdissection

  • Liane Fendt
  • Harald Niederstätter
  • Gabriela Huber
  • Bettina Zelger
  • Martina Dünser
  • Christof Seifarth
  • Alexander Röck
  • Georg Schäfer
  • Helmut Klocker
  • Walther Parson
Preclinical study


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.


Mitochondrial DNA Breast cancer Mutation Microdissection Phylogeny 



Mitochondrial DNA


Laser capture microdissection


NADH dehydrogenase


Cytochrome oxidase


Cytochrome b


Oxidative phosphorylation



AR and WP were supported by the FWF Austrian Science Fund Translational Research Programme (L397). We are grateful to o.Univ.-Prof. Dr. Raimund Margreiter (Department of Operative Medicine, Innsbruck Medical University) for supporting the study.

Supplementary material

10549_2010_1092_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 32 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Liane Fendt
    • 1
  • Harald Niederstätter
    • 1
  • Gabriela Huber
    • 1
  • Bettina Zelger
    • 2
  • Martina Dünser
    • 4
  • Christof Seifarth
    • 2
  • Alexander Röck
    • 5
  • Georg Schäfer
    • 3
  • Helmut Klocker
    • 3
  • Walther Parson
    • 1
  1. 1.Institute of Legal MedicineInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Institute of PathologyInnsbruck Medical UniversityInnsbruckAustria
  3. 3.Experimental UrologyInnsbruck Medical UniversityInnsbruckAustria
  4. 4.Department of Operative MedicineInnsbruck Medical UniversityInnsbruckAustria
  5. 5.Institute of MathematicsUniversity of InnsbruckInnsbruckAustria

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