Tumor-Specific Mitochondrial DNA Variants Are Rarely Detected in Cell-Free DNA

Neoplasia : an International Journal for Oncology Research
Marjolein Ja WeertsJohn Wm Martens

Abstract

The use of blood-circulating cell-free DNA (cfDNA) as a "liquid biopsy" in oncology is being explored for its potential as a cancer biomarker. Mitochondria contain their own circular genomic entity (mitochondrial DNA, mtDNA), up to even thousands of copies per cell. The mutation rate of mtDNA is several orders of magnitude higher than that of the nuclear DNA. Tumor-specific variants have been identified in tumors along the entire mtDNA, and their number varies among and within tumors. The high mtDNA copy number per cell and the high mtDNA mutation rate make it worthwhile to explore the potential of tumor-specific cf-mtDNA variants as cancer marker in the blood of cancer patients. We used single-molecule real-time (SMRT) sequencing to profile the entire mtDNA of 19 tissue specimens (primary tumor and/or metastatic sites, and tumor-adjacent normal tissue) and 9 cfDNA samples, originating from 8 cancer patients (5 breast, 3 colon). For each patient, tumor-specific mtDNA variants were detected and traced in cfDNA by SMRT sequencing and/or digital PCR to explore their feasibility as cancer biomarker. As a reference, we measured other blood-circulating biomarkers for these patients, including driver mutations in nuclear-encoded cfDNA...Continue Reading

Citations

Nov 28, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Gabriela L OliveiraPaulo J Oliveira
May 18, 2021·Frontiers in Oncology·Anastasia P KovalDmitry S Shcherbo
Jul 25, 2021·International Journal of Molecular Sciences·Carlos Jhovani Pérez-AmadoSilvia Jiménez-Morales
Sep 24, 2021·Veterinary and Comparative Oncology·Krzysztof KowalBrygida Ślaska

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Methods Mentioned

BETA
blood draw
PCR
electrophoresis
genotyping

Software Mentioned

HaploGrep2
Integrative Genomics Viewer ( IGV )
Sequel
BWA
Bioconductor Rsamtools
rCRS
MEM
BLAST
SMRTbell
Cutadapt

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