A critical reassessment of the role of mitochondria in tumorigenesis.
BACKGROUND
Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results.


RESULTS
In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis.


CONCLUSIONS
The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.
Salas
Antonio
A
Unidade de Xenética, Instituto de Medicina Legal, Facultade de Medicina, Universidad de Santiago de Compostela, Galicia, Spain. apimlase@usc.es
Yao
Yong-Gang
YG
Macaulay
Vincent
V
Vega
Ana
A
Carracedo
Angel
A
Bandelt
Hans-Jürgen
HJ
D016477:Artifacts; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D030561:Databases, Nucleic Acid; D003951:Diagnostic Errors; D005826:Genetics, Medical; D006239:Haplotypes; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D015203:Reproducibility of Results; D012107:Research Design
D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial