Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?

Edoardo Errichiello, Tiziana Venesio

Research output: Contribution to journalReview article

Abstract

Introduction: 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. Findings: 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.

Original languageEnglish
Pages (from-to)1905-1914
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume143
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • Cancer therapy
  • Colorectal carcinogenesis
  • D-loop
  • Heteroplasmy
  • Mitochondrial DNA variants
  • mtDNA copy number alterations
  • Nuclear-mitochondrial crosstalk
  • Oxidative stress

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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