title: Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?
abstract: BACKGROUND
  Mitochondrial DNA alterations have widely been reported in many age-related degenerative diseases and tumors, including colorectal cancer. In the past few years, the discovery of inter-genomic crosstalk between nucleus and mitochondria has reinforced the role of mitochondrial DNA variants in perturbing this essential signaling pathway and thus indirectly targeting nuclear genes involved in tumorigenic and invasive phenotype.
  
  
  RESULTS
  Mitochondrial dysfunction is currently considered a crucial hallmark of carcinogenesis as well as a promising target for anticancer therapy. Mitochondrial DNA alterations include point mutations, deletions, inversions, and copy number variations, but numerous studies investigating their pathogenic role in cancer have provided inconsistent evidence. Furthermore, the biological impact of mitochondrial DNA variants may vary tremendously, depending on the proportion of mutant DNA molecules carried by the neoplastic cells (heteroplasmy).
  
  
  CONCLUSIONS
  In this review, we discuss the role of different type of mitochondrial DNA alterations in colorectal carcinogenesis and, in particular, we revisit the issue of whether they may be considered as causative driver or simply genuine passenger events. The advent of high-throughput techniques as well as the development of genetic and pharmaceutical interventions for the treatment of mitochondrial dysfunction in colorectal cancer are also explored.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100, Pavia, Italy. edoardo.errichiello01@universitadipavia.it.|Molecular Pathology Laboratory, Unit of Pathology, Candiolo Cancer Institute, FPO-IRCCS, Starda Provinciale 142, Candiolo, 10060, Turin, Italy. edoardo.errichiello01@universitadipavia.it.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Errichiello
authors.affiliation: Molecular Pathology Laboratory, Unit of Pathology, Candiolo Cancer Institute, FPO-IRCCS, Starda Provinciale 142, Candiolo, 10060, Turin, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Venesio
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial
keywords: Cancer therapy; Colorectal carcinogenesis; D-loop; Heteroplasmy; Mitochondrial DNA variants; Nuclear-mitochondrial crosstalk; Oxidative stress; mtDNA copy number alterations