Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers

Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. To ascertain the role of frequent somatic genomic alter...

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Published in:European journal of cancer (1990) 2023-05, Vol.185, p.105-118
Main Authors: Lozano, Rebeca, Castro, Elena, Lopez-Campos, Fernando, Thorne, Heather, Ramirez-Backhaus, Miguel, Aragon, Isabel M., Cendón-Florez, Ylenia, Gutierrez-Pecharroman, Ana, Salles, Daniela C., Romero-Laorden, Nuria, Lorente, David, González-Peramato, Pilar, Calatrava, Ana, Alonso, Concepción, Anido, Urbano, Arévalo-Lobera, Sara, Balmaña, Judith, Chirivella, Isabel, Juan-Fita, María José, Llort, Gemma, y Cajal, Teresa Ramón, Almagro, Elena, Alameda, Daniel, López-Casas, Pedro P., Herrera, Bernardo, Mateo, Joaquin, Pritchard, Colin C., Antonarakis, Emmanuel S., Lotan, Tamara L., Rubio-Briones, José, Sandhu, Shahneen, Olmos, David
Format: Article
Language:English
Subjects:
BRCA2
BRCA2 Protein - genetics
Disease progression
DNA Copy Number Variations
Germ Cells - pathology
Germ-Line Mutation
Germline
Heterozygote
Humans
Male
Mutation
Prostate cancer
Prostatic Neoplasms - pathology
Survival outcomes
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Summary:Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN. Presence of intraductal and cribriform subtypes was also assessed. The independent impact of these events on cause-specific survival (CSS), metastasis-free survival and time to castration-resistant disease was assessed using cox-regression models. Somatic BRCA2-RB1 co-deletion (41% versus 12%, p 
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2023.02.022