Cancer and meiotic gene expression: Two sides of the same coin?

Abstract

Meiosis increases genetic diversity in offspring by generating genetically unique haploid gametes with reshuffled chromosomes. This process requires a specialized set of meiotic proteins, which facilitate chromosome recombination and segregation. However, re-expression of meiotic proteins in mitosis can have catastrophic oncogenic consequences and aberrant expression of meiotic proteins is a common occurrence in human tumors. Mechanistically, re-activation of meiotic genes in cancer promotes oncogenesis likely because cancers-conversely to healthy mitosis-are fueled by genetic instability which promotes tumor evolution, and evasion of immune response and treatment pressure. In this review, we explore similarities between meiotic and cancer cells with a particular focus on the oncogenic activation of meiotic genes in cancer. We emphasize the role of histones and their modifications, DNA methylation, genome organization, R-loops and the availability of distal enhancers.

Keywords: Cancer; Cancer testis antigen; Chromatin; Germ cell cancer gene; Meiosis; R-loop; Synaptonemal complex; TAD; Topologically associated domain; Transcription.