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Loss of chromosome Y in primary tumors

View ORCID ProfileMeifang Qi, Jiali Pang, Irene Mitsiades, View ORCID ProfileAndrew A. Lane, View ORCID ProfileEsther Rheinbay
doi: https://doi.org/10.1101/2022.08.22.504831
Meifang Qi
1Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129
2Harvard Medical School, Boston, MA 02215
3Broad Institute of MIT and Harvard, Cambridge, MA 02139
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  • ORCID record for Meifang Qi
Jiali Pang
1Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129
4Harvard T.H. Chan School of Public Health, Boston, MA 02115
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Irene Mitsiades
1Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129
2Harvard Medical School, Boston, MA 02215
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Andrew A. Lane
2Harvard Medical School, Boston, MA 02215
3Broad Institute of MIT and Harvard, Cambridge, MA 02139
5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115
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Esther Rheinbay
1Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129
2Harvard Medical School, Boston, MA 02215
3Broad Institute of MIT and Harvard, Cambridge, MA 02139
6Massachusetts General Hospital Department of Pathology, Boston, MA 02114
6Massachusetts General Hospital Department of Pathology, Boston, MA 02114
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  • For correspondence: esther@broadinstitute.org
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Abstract

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 Statement

AAL is a consultant for Qiagen. AAL received research support from AbbVie and Stemline Therapeutics.

Footnotes

  • Contact: erheinbay{at}mgh.harvard.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 22, 2022.
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Loss of chromosome Y in primary tumors
Meifang Qi, Jiali Pang, Irene Mitsiades, Andrew A. Lane, Esther Rheinbay
bioRxiv 2022.08.22.504831; doi: https://doi.org/10.1101/2022.08.22.504831
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Loss of chromosome Y in primary tumors
Meifang Qi, Jiali Pang, Irene Mitsiades, Andrew A. Lane, Esther Rheinbay
bioRxiv 2022.08.22.504831; doi: https://doi.org/10.1101/2022.08.22.504831

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