Recurrent deletions and regulatory disruption of the Y chromosome in cancer.

Recurrent euchromatic deletions on the Y chromosome in male cancers are linked to altered gene regulation and clinical outcomes, highlighting their functional significance.

• Why it matters: Loss of the Y chromosome (LOY) is common in aging males and across various cancers, but its precise role in tumor development and progression remains unclear, especially regarding partial deletions.
• What they did: Using high-coverage whole-genome sequencing, transcriptomics, and eQTL analysis on male cancer cell lines, the study mapped LOY patterns, developed the YES Score to quantify deletions, and examined their impact on gene expression.
• The result: Findings show that LOY involves specific euchromatic deletions affecting coding and non-coding regions, with retained Y loci remaining active and associated with key cellular functions, suggesting LOY's regulatory and clinical importance.