Catch Me If You Can: Could Y Chromosome Loss Spread in Cancer?

Abstract The recent surge in studies of loss of the Y chromosome (LOY) in cancer has challenged long-standing assumptions about the Y chromosome as largely dispensable outside of sex determination and spermatogenesis. In the latest paper, the labs of Knott and Theodorescu present provocative evidence suggesting that LOY in tumor cells correlates with LOY in tumor-infiltrating immune cells and, most unexpectedly, that LOY may be "contagious" within the tumor microenvironment. These findings, while intriguing, demand cautious interpretation and rigorous validation. Notably, while the authors observe correlation between tumor LOY and stromal LOY, the causal mechanisms remain obscure. Moreover, the notion that LOY can be induced in non-malignant immune cells by LOY tumor cells warrants both excitement and further experimental scrutiny. Nonetheless, this study serves as a catalyst for renewed interest in the functional relevance of the Y chromosome in cancer and aging. As Darwin alluded, sexuality and its chromosomal determinants remain among biology's deepest mysteries. The current work opens a new chapter in this exploration, albeit one that must be read with both curiosity and scientific rigor.