Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets Journal Article
| Authors: | Tang, F.; Xu, D.; Wang, S.; Wong, C. K.; Martinez-Fundichely, A.; Lee, C. J.; Cohen, S.; Park, J.; Hill, C. E.; Eng, K.; Bareja, R.; Han, T.; Liu, E. M.; Palladino, A.; Di, W.; Gao, D.; Abida, W.; Beg, S.; Puca, L.; Meneses, M.; de Stanchina, E.; Berger, M. F.; Gopalan, A.; Dow, L. E.; Mosquera, J. M.; Beltran, H.; Sternberg, C. N.; Chi, P.; Scher, H. I.; Sboner, A.; Chen, Y.; Khurana, E. |
| Article Title: | Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets |
| Abstract: | In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing to investigate 22 organoids, six patient-derived xenografts, and 12 cell lines. We identified the well-characterized AR-dependent and neuroendocrine subtypes, as well as two AR-negative/low groups: a Wnt-dependent subtype, and a stem cell-like (SCL) subtype driven by activator protein-1 (AP-1) transcription factors. We used transcriptomic signatures to classify 366 patients, which showed that SCL is the second most common subtype of CRPC after AR-dependent. Our data suggest that AP-1 interacts with the YAP/TAZ and TEAD proteins to maintain subtype-specific chromatin accessibility and transcriptomic landscapes in this group. Together, this molecular classification reveals drug targets and can potentially guide therapeutic decisions. © 2022 American Association for the Advancement of Science. All rights reserved. |
| Keywords: | genetics; androgen; metabolism; cell line, tumor; dna; chromatin; tumor cell line; androgen receptor; castration; receptors, androgen; castration resistant prostate cancer; cell; drug; transcription factor ap 1; transcription factor ap-1; cell component; cancer; humans; human; male; prostatic neoplasms, castration-resistant |
| Journal Title: | Science |
| Volume: | 376 |
| Issue: | 6596 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2022-05-27 |
| Start Page: | eabe1505 |
| Language: | English |
| DOI: | 10.1126/science.abe1505 |
| PUBMED: | 35617398 |
| PROVIDER: | scopus |
| PMCID: | PMC9299269 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2022 -- Source: Scopus |
