Potential pitfalls in MitoChip detected tumor-specific somatic mutations: a call for caution when interpreting patient data

BMC Cancer. 2010 Oct 30:10:597. doi: 10.1186/1471-2407-10-597.


Background: Several investigators have employed high throughput mitochondrial sequencing array (MitoChip) in clinical studies to search mtDNA for markers linked to cancers. In consequence, a host of somatic mtDNA mutations have been identified as linked to different types of cancers. However, closer examination of these data show that there are a number of potential pitfalls in the detection tumor-specific somatic mutations in clinical case studies, thus urging caution in the interpretation of mtDNA data to the patients. This study examined mitochondrial sequence variants demonstrated in cancer patients, and assessed the reliability of using detected patterns of polymorphisms in the early diagnosis of cancer.

Methods: Published entire mitochondrial genomes from head and neck, adenoid cystic carcinoma, sessile serrated adenoma, and lung primary tumor from clinical patients were examined in a phylogenetic context and compared with known, naturally occurring mutations which characterize different populations.

Results: The phylogenetic linkage analysis of whole arrays of mtDNA mutations from patient cancerous and non-cancerous tissue confirmed that artificial recombination events occurred in studies of head and neck, adenoid cystic carcinoma, sessile serrated adenoma, and lung primary tumor. Our phylogenetic analysis of these tumor and control leukocyte mtDNA haplotype sequences shows clear cut evidence of mixed ancestries found in single individuals.

Conclusions: Our study makes two prescriptions: both in the clinical situation and in research 1. more care should be taken in maintaining sample identity and 2. analysis should always be undertaken with respect to all the data available and within an evolutionary framework to eliminate artifacts and mix-ups.

MeSH terms

  • Adenoma / genetics
  • Carcinoma, Adenoid Cystic / genetics
  • DNA, Mitochondrial / genetics*
  • Genetic Techniques
  • Genome
  • Head and Neck Neoplasms / genetics
  • Humans
  • Mutation*
  • Neoplasms / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Phylogeny
  • Polymorphism, Genetic*
  • Reactive Oxygen Species


  • DNA, Mitochondrial
  • Reactive Oxygen Species