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Byline: S. Sinha, S. Siriguri, S. Kanakmedala, K. Bikkasani Aims: To review prostatic biopsy findings in Indian patients with elevated serum prostate-specific antigen (PSA) attending the Urology department at a [...]

Condensin is a multi-subunit structural maintenance of chromosomes (SMC) complex that binds to and compacts chromosomes. Here, we addressed the regulation of condensin binding dynamics using Caenorhabditis elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes DPY-27 binding to X chromosomes. Next, we performed FRAP in the background of several chromatin modifier mutants that cause varying degrees of X chromosome derepression. The greatest effect was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of condensin DC reduced from ∼30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Hi-C sequencing data from the dpy-21 null mutant showed little change compared to wild-type data, uncoupling Hi-C-measured long-range DNA contacts from transcriptional repression of the X chromosomes. Taken together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background: Prostate-specific antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer; however, the significance of PSA at or near the time of death is not well understood. This study aimed to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC)., Patients and Methods: The Mount Sinai Genitourinary Cancer Biorepository, an institutional review board-approved, single-institution database containing all consented genitourinary cancer patients seen between 2010 and 2018, was used to identify and stratify patients into the following cohorts based on their PSA at or near death: <100 ng/mL, 100-1000 ng/mL, and >1000 ng/mL. Analyses were performed to assess clinical characteristics of disease, treatment response, and outcomes., Results: We identified 1097 patients with prostate cancer, and 101 were confirmed to be deceased following a diagnosis of mCRPC. In patients with mCRPC, cohorts of higher PSA level at death were associated with lower Gleason score at diagnosis and a trend toward longer time to mCRPC and longer time from diagnosis to death, despite a higher burden of disease at death. Conversely, subgroup analysis of PSA < 10 ng/mL at death was associated with lower rates of imaging within 6 months of death, lower treatment rate, and worse clinical outcomes., Conclusions: Cohorts of different PSA levels at death in mCRPC patients showed distinct patterns of disease characteristics and clinical outcomes, likely due to the underlying molecular phenotype differences. Imaging for the patient population with very low PSA levels may be underutilized and should be considered more routinely., (Copyright © 2021 Elsevier Inc. All rights reserved.)