Since the human genome contains about 6% of tumor suppressor genes (TSGs) and the X chromosome alone holds a substantial share (2%), herein, we have discussed exclusively the relative contribution of X-linked human TSGs that appear to be primarily involved in 32 different cancer types. Our analysis showed that, (a) the majority of X-linked TSGs are primarily involved in the dysregulation of breast cancer, followed by prostate cancer, (b) Despite being escaped from X chromosome inactivation (XCI), a clear pattern of altered promoter methylation linked to the mutational burden was observed among them. (c) X-linked TSGs (mainly on the q-arm) maintain spatial and genetic interactions with certain autosomal loci. Corroborating our previous findings that loss/gain of entire sex chromosomes (in XO and XXY syndromes) can profoundly affect the epigenetic status of autosomes we herein suggest that X-linked TSGs alone can also contribute significantly in the dynamics this sex chromosome-autosome crosstalk to restructure the cancer genome.
Keywords: DNA methylation; X chromosome; cancer; evolution; tumor suppressor genes.