Loss of the Y chromosome as a driver of cancer
Description: Gender and biological sex are both associated with differences in incidence, outcome and response to therapy between men and women with cancer. Aside from differences in exposures and hormones, the tumors of men have X and Y sex chromosomes, while female tumors have two X chromosomes. As a small chromosome, Y is lost easily from cells, both in tumors and in normal blood cells of aging men. Loss of Y (LOY) in blood has been shown to be associated with overall mortality, heart disease, and importantly, cancer. We have previously developed methods to measure loss of Y (LOY) in tumors from genomic data and found that LOY is associated with poor outcome in some cancer types. This could be due to loss of several tumor suppressor genes on the Y chromosome. Our long-term goal is to improve health care based on tumor sex, exploiting genetic vulnerabilities created by the different combination of sex chromosomes and LOY. In this proposal, we aim to find the exact genes that drive LOY with deep genomic analysis, and the cellular changes that are caused by LOY. Finally, we recognize that research into LOY in the blood has been largely biased towards men of European ancestry. Using the new NIH’s All of Us Research Program data, which has collected data from participants of diverse ancestries, we propose to study the frequency and health outcomes linked to LOY in men of different ancestries.
Funder: American Cancer Society
Amount: $960,000
Funding type: award
Start date: 2024-07-01
End date: 2028-06-30
Investigator: Esther Rheinbay
Institution: Massachusetts General Hospital (Mass General)
Subfield: Genetics
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: RSG-24-1257286-01-CCB
OpenAlex ID: G6161450520