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

前列腺癌 生物 Y染色体 染色体 癌症 17号染色体(人) 核型 4号染色体 癌症研究 遗传学 基因
作者
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
出处
期刊:PLOS ONE [Public Library of Science]
卷期号:19 (4): e0301989-e0301989
标识
DOI:10.1371/journal.pone.0301989
摘要

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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