Qi Meifang, Pang Jiali, Mitsiades Irene, Lane Andrew A, Rheinbay Esther
Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129, USA; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Cell. 2023 Jun 22. doi: 10.1016/j.cell.2023.06.006.
Certain cancer types afflict female and male patients disproportionately. The reasons include differences in male/female physiology, effect of sex hormones, risk behavior, environmental exposures, and genetics of the sex chromosomes X and Y. Loss of Y (LOY) is common in peripheral blood cells in aging men, and this phenomenon is associated with several diseases. However, the frequency and role of LOY in tumors is little understood. Here, we present a comprehensive catalog of LOY in >5,000 primary tumors from male patients in the TCGA. We show that LOY rates vary by tumor type and provide evidence for LOY being either a passenger or driver event depending on context. LOY in uveal melanoma specifically is associated with age and survival and is an independent predictor of poor outcome. LOY creates common dependencies on DDX3X and EIF1AX in male cell lines, suggesting that LOY generates unique vulnerabilities that could be therapeutically exploited.
某些癌症类型对女性和男性患者的影响程度差异很大。原因包括男女生理差异、性激素的作用、风险行为、环境暴露以及X和Y性染色体的遗传学。Y染色体缺失（LOY）在老年男性的外周血细胞中很常见，这种现象与多种疾病有关。然而，LOY在肿瘤中的频率和作用却鲜为人知。在此，我们展示了来自TCGA中5000多名男性患者原发性肿瘤中LOY的综合目录。我们表明，LOY发生率因肿瘤类型而异，并根据具体情况为LOY是过客事件还是驱动事件提供了证据。葡萄膜黑色素瘤中的LOY尤其与年龄和生存率相关，并且是预后不良的独立预测指标。LOY在男性细胞系中对DDX3X和EIF1AX产生共同依赖性，这表明LOY产生了独特的脆弱性，可用于治疗开发。
