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.
PloS one. 2024 Apr 29*** epublish ***
Sai Harisha Rajanala, Romina Ghale, Subhiksha Nandakumar, Kalyani Chadalavada, Gwo-Shu Mary Lee, Konrad H Stopsack, Yu Chen, Gouri J Nanjangud, Goutam Chakraborty, Philip W Kantoff
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America., Molecular Cytogenetics Core, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Masacheussets, United States of America.