Cancer testis antigens and genomic instability: More than immunology

Cancer testis antigens or genes (CTA, CTG) are predominantly expressed in adult testes while silenced in most or all somatic tissues with sporadic expression in many human cancers. Concerted misexpression of numerous CTA/CTGs is rarely observed. This finding argues against the germ cell theory of cancer. A surprising number of CTA/CTGs are involved in meiotic chromosome metabolism and specifically in meiotic recombination. Recent discoveries with a group of CTGs established that their misexpression in somatic cells results in genomic instability by interfering with homologous recombination (HR), a DNA repair pathway for complex DNA damage such as DNA double-stranded breaks, interstrand crosslinks, and single-stranded DNA gaps. HR-deficient tumors have specific vulnerabilities and show synthetic lethality with inhibition of polyADP-ribose polymerase, opening the possibility that expression of CTA/CTGs that result in an HR-defect could be used as an additional biomarker for HR status. Here, we review the repertoire of CTA/CTGs focusing on a cohort that functions in meiotic chromosome metabolism by interrogating relevant cancer databases and discussing recent discoveries.