Quantifying Y chromosome loss in primary and metastatic prostate cancer by chromosome painting.

Somatic Y chromosome loss in hematopoietic cells is associated with higher mortality in men. However, the status of the Y chromosome in cancer tissue is not fully known due to technical limitations, such as difficulties in labelling and sequencing DNA from the Y chromosome. We have developed a system to quantify Y chromosome gain or loss in patient-derived prostate cancer organoids. Using our system, we observed Y chromosome loss in 4 of the 13 (31%) patient-derived metastatic castration-resistant prostate cancer (mCRPC) organoids; interestingly, loss of Yq (long arm of the Y chromosome) was seen in 38% of patient-derived organoids. Additionally, potential associations were observed between mCRPC and Y chromosome nullisomy. The prevalence of Y chromosome loss was similar in primary and metastatic tissue, suggesting that Y chromosome loss is an early event in prostate cancer evolution and may not a result of drug resistance or organoid derivation. This study reports quantification of Y chromosome loss and gain in primary and metastatic prostate cancer tissue and lays the groundwork for further studies investigating the clinical relevance of Y chromosome loss or gain in mCRPC.

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Copyright: © 2024 Rajanala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

Sai Harisha Rajanala: No competing interests to declare. Romina Ghale: No competing interests to declare. Subhiksha Nandakumar: No competing interests to declare. Kalyani Chadalavada: No competing interests to declare. Gwo-Shu Mary Lee: No competing interests to declare. Konrad H. Stopsack: No competing interests to declare. Yu Chen: No competing interests to declare. Gouri J. Nanjangud: No competing interests to declare. Goutam Chakraborty: Has served as a scientific consultant for GuidePoint and received consultation fees. Philip W. Kantoff: The author has financial interest in Convergent Therapeutics, Inc., Context Therapeutics Inc., and ESSA Pharma Inc. He is a member of the Board of Directors for Convergent Therapeutics, Inc., Context Therapeutics Inc., and ESSA Pharma Inc. He is a consultant/member of the Scientific Advisory Board for Immunis.AI and PrognomIQ. The author has no other competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.