Partial Y chromosome loss alters gene activity in cancer cells
Genomic analysis of male cancer cell lines reveals recurrent partial Y chromosome deletions linked to altered gene expression and clinical outcome patterns.
Communications Biology
In a study of male cancer cell lines, researchers investigated whether loss of the Y chromosome involves complex partial deletions rather than simple binary loss. Using high-coverage whole-genome sequencing, transcriptomics, and eQTL mapping, the team examined male cell lines to eliminate confounding signals from non-malignant cells.
The analysis revealed a region-specific landscape of recurrent euchromatic deletions affecting both protein-coding genes and non-coding elements. To measure these alterations, the researchers established the Y EroSion (YES) Score. This score tracked with transcriptional differences and clinical outcome patterns suggestive of functional relevance. Furthermore, retained Y-linked loci remained transcriptionally active, displaying enrichment for cell proliferation, immune signaling, and stress adaptation functions.
Why it matters
Loss of the Y chromosome is the most frequent acquired genomic alteration in aging males. Uncovering how partial deletions drive downstream gene regulation helps clarify the functional role of this age-related genomic change across male cancers.
Caveats
The study was conducted in cancer cell lines rather than patient tissues, and the authors state that the findings require validation in primary tumor cohorts.
The paper
Recurrent deletions and regulatory disruption of the Y chromosome in cancer
Cedars-Sinai Medical Center · University of Arizona
Communications Biology · 28 Sep 2026 · CC BY-NC-ND