X-Linked Tumor Suppressor Genes Act as Presumed Contributors in the Sex Chromosome-Autosome Crosstalk in Cancers

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.

人类基因组中约有6%为肿瘤抑制基因（tumor suppressor genes, TSGs），仅X染色体就占据了其中可观的2%份额。据此，本文仅聚焦于X连锁型人类肿瘤抑制基因的相对贡献，这类基因主要参与32种不同癌症的致病过程。本研究分析显示：(a) 绝大多数X连锁型肿瘤抑制基因主要与乳腺癌的调控异常相关，其次为前列腺癌；(b) 尽管这类基因可逃逸X染色体失活（X chromosome inactivation, XCI），但本研究在其中观测到与突变负荷相关的启动子甲基化改变的明确模式；(c) X连锁型肿瘤抑制基因（主要位于q臂区域）可与特定常染色体位点维持空间及遗传互作。本研究佐证了此前的发现——整条性染色体的缺失/扩增（见于XO综合征与XXY综合征）可显著影响常染色体的表观遗传状态；据此我们提出，仅X连锁型肿瘤抑制基因即可在性染色体-常染色体串扰的动态过程中发挥重要作用，进而参与癌症基因组的重构。