New hypotheses for large-scale epigenome alterations in somatic cancer cells: a role for male germ-cell-specific regulators.

Oncogenic cell transformation is consistently associated with alterations of the cell epigenome leading to aberrant gene repression and activation. Some of these events, such as the DNA-methylation-based silencing of tumor suppressor genes, are considered to be oncogenic themselves. A much less-studied consequence of these epigenetic misregulations is the abnormal activation of tissue-specific genes in precancerous and transformed cells. Here, we explore the idea that the aberrant expression of germ-cell-specific genes in somatic cancer cells could contribute to malignant cell transformation and cancer progression. Indeed, a significant number of papers have reported the abnormal activation of germ cell-specific genes in various somatic cancers (known as cancer testis [C/T] antigens or factors). Although in most cases the physiological function of these genes remains unknown, functional investigations suggest that they can act as potent genome, epigenome and cellular reorganizers. Hence, in view of the existing literature, we discuss the hypothesis that C/T activation in somatic cells is not only a consequence of global epigenetic deregulation, but also a cause of further large-scale alterations of the epigenome, which themselves have direct oncogenic consequences for the affected cells. Finally, we highlight the fact that C/T factors have the potential to serve as valuable markers for cancer detection, as well as provide promising targets for developing new therapeutical strategies.