TY - JOUR
T1 - Heteroplasmic mitochondrial DNA mutations in normal and tumour cells
AU - He, Yiping
AU - Wu, Jian
AU - Dressman, Devin C.
AU - Iacobuzio-Donahue, Christine
AU - Markowitz, Sanford D.
AU - Velculescu, Victor E.
AU - Diaz, Luis A.
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Papadopoulos, Nickolas
N1 - Funding Information:
Acknowledgements We thank M. Whalen, J. Ptak, L. Dobbyn and N. Silliman for expert technical assistance. This work was supported by The Virginia and D. K. Ludwig Fund for Cancer Research and by National Institutes of Health grants CA57345, CA 43460, CA 62924 and CA121113.
PY - 2010/3/25
Y1 - 2010/3/25
N2 - The presence of hundreds of copies of mitochondrial DNA (mtDNA) in each human cell poses a challenge for the complete characterization of mtDNA genomes by conventional sequencing technologies. Here we describe digital sequencing of mtDNA genomes with the use of massively parallel sequencing-by-synthesis approaches. Although the mtDNA of human cells is considered to be homogeneous, we found widespread heterogeneity (heteroplasmy) in the mtDNA of normal human cells. Moreover, the frequency of heteroplasmic variants varied considerably between different tissues in the same individual. In addition to the variants identified in normal tissues, cancer cells harboured further homoplasmic and heteroplasmic mutations that could also be detected in patient plasma. These studies provide insights into the nature and variability of mtDNA sequences and have implications for mitochondrial processes during embryogenesis, cancer biomarker development and forensic analysis. In particular, they demonstrate that individual humans are characterized by a complex mixture of related mitochondrial genotypes rather than a single genotype.
AB - The presence of hundreds of copies of mitochondrial DNA (mtDNA) in each human cell poses a challenge for the complete characterization of mtDNA genomes by conventional sequencing technologies. Here we describe digital sequencing of mtDNA genomes with the use of massively parallel sequencing-by-synthesis approaches. Although the mtDNA of human cells is considered to be homogeneous, we found widespread heterogeneity (heteroplasmy) in the mtDNA of normal human cells. Moreover, the frequency of heteroplasmic variants varied considerably between different tissues in the same individual. In addition to the variants identified in normal tissues, cancer cells harboured further homoplasmic and heteroplasmic mutations that could also be detected in patient plasma. These studies provide insights into the nature and variability of mtDNA sequences and have implications for mitochondrial processes during embryogenesis, cancer biomarker development and forensic analysis. In particular, they demonstrate that individual humans are characterized by a complex mixture of related mitochondrial genotypes rather than a single genotype.
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U2 - 10.1038/nature08802
DO - 10.1038/nature08802
M3 - Article
C2 - 20200521
AN - SCOPUS:77950083955
SN - 0028-0836
VL - 464
SP - 610
EP - 614
JO - Nature
JF - Nature
IS - 7288
ER -