Single-cell mtDNA heteroplasmy in colorectal cancer

Genomics. 2022 Mar;114(2):110315. doi: 10.1016/j.ygeno.2022.110315. Epub 2022 Feb 16.


Human mitochondria can be genetically distinct within the same individual, a phenomenon known as heteroplasmy. In cancer, this phenomenon seems exacerbated, and most mitochondrial mutations seem to be heteroplasmic. How this genetic variation is arranged within and among normal and tumor cells is not well understood. To address this question, here we sequenced single-cell mitochondrial genomes from multiple normal and tumoral locations in four colorectal cancer patients. Our results suggest that single cells, both normal and tumoral, can carry various mitochondrial haplotypes. Remarkably, this intra-cell heteroplasmy can arise before tumor development and be maintained afterward in specific tumoral cell subpopulations. At least in the colorectal patients studied here, the somatic mutations in the single-cells do not seem to have a prominent role in tumorigenesis.

Keywords: Intracellular heteroplasmy; Single-cell mitochondrial genomics; mtDNA homoplasmy; scDNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms* / genetics
  • DNA, Mitochondrial* / genetics
  • Haplotypes
  • Heteroplasmy
  • Humans
  • Mitochondria / genetics


  • DNA, Mitochondrial