TY - JOUR T1 - Loss of chromosome Y in primary tumors JF - bioRxiv DO - 10.1101/2022.08.22.504831 SP - 2022.08.22.504831 AU - Meifang Qi AU - Jiali Pang AU - Irene Mitsiades AU - Andrew A. Lane AU - Esther Rheinbay Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/08/22/2022.08.22.504831.abstract N2 - It has long been recognized that certain cancer types afflict female and male patients disproportionately. The reasons for this disparity include differences in male/female physiology, effect of sex hormones, risk behavior and environmental exposures, and different copy number 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, 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.Competing Interest StatementAAL is a consultant for Qiagen. AAL received research support from AbbVie and Stemline Therapeutics. ER -