RT Journal Article
SR Electronic
T1 Loss of chromosome Y in primary tumors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.22.504831
DO 10.1101/2022.08.22.504831
A1 Meifang Qi
A1 Jiali Pang
A1 Irene Mitsiades
A1 Andrew A. Lane
A1 Esther Rheinbay
YR 2022
UL http://biorxiv.org/content/early/2022/08/22/2022.08.22.504831.abstract
AB 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.