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Data from SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity

Authors :
Johann S. de Bono
Joaquin Mateo
Suzanne Carreira
Christopher E. Barbieri
Wei Yuan
Mark A. Rubin
Theresa MacDonald
Adam Sharp
Jane Goodall
Matthew Clarke
Mark Atkin
Flavia M. de Oliveira
Claudia Bertan
Sara Aziz
Veronica Gil
Rossitza Christova
Ana Ferreira
Inês Figueiredo
Susana Miranda
Nina Tunariu
Raquel Perez-Lopez
Deirdre Moloney
Joanne Hunt
Diletta Bianchini
Semini Sumanasuriya
Zafeiris Zafeiriou
Mateus Crespo
Ruth Riisnaes
David Dolling
George Seed
Pasquale Rescigno
Daniel N. Rodrigues
Gunther Boysen
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

Abstract

Purpose: CHD1 deletions and SPOP mutations frequently cooccur in prostate cancer with lower frequencies reported in castration-resistant prostate cancer (CRPC). We monitored CHD1 expression during disease progression and assessed the molecular and clinical characteristics of CHD1-deleted/SPOP-mutated metastatic CRPC (mCRPC).Experimental Design: We identified 89 patients with mCRPC who had hormone-naive and castration-resistant tumor samples available: These were analyzed for CHD1, PTEN, and ERG expression by IHC. SPOP status was determined by targeted next-generation sequencing (NGS). We studied the correlations between these biomarkers and (i) overall survival from diagnosis; (ii) overall survival from CRPC; (iii) duration of abiraterone treatment; and (iv) response to abiraterone. Relationship with outcome was analyzed using Cox regression and log-rank analyses.Results: CHD1 protein loss was detected in 11 (15%) and 13 (17%) of hormone-sensitive prostate cancer (HSPC) and CRPC biopsies, respectively. Comparison of CHD1 expression was feasible in 56 matched, same patient HSPC and CRPC biopsies. CHD1 protein status in HSPC and CRPC correlated in 55 of 56 cases (98%). We identified 22 patients with somatic SPOP mutations, with six of these mutations not reported previously in prostate cancer. SPOP mutations and/or CHD1 loss was associated with a higher response rate to abiraterone (SPOP: OR, 14.50 P = 0.001; CHD1: OR, 7.30, P = 0.08) and a longer time on abiraterone (SPOP: HR, 0.37, P = 0.002, CHD1: HR, 0.50, P = 0.06).Conclusions: SPOP-mutated mCRPCs are strongly enriched for CHD1 loss. These tumors appear highly sensitive to abiraterone treatment. Clin Cancer Res; 24(22); 5585–93. ©2018 AACR.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....865aeff6b8bdf18f199c9c3e24ee6798