Highlights
- •gBRCA2 prostate tumours are enriched in BRCA2-RB1 co-deletion and MYC amplification.
- •Outcomes of gBRCA2 carriers are influenced by the presence/absence of these events.
- •Integration of germline and somatic information would refine prognosis estimations.
Abstract
Background
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.
Patients and methods
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.
Results
Somatic BRCA2-RB1 co-deletion (41% versus 12%, p < 0.001) and MYC amplification (53.4% versus 18.8%, p < 0.001) were enriched in gBRCA2 compared to sporadic tumours. Median CSS from diagnosis of PCa was 9.1 versus 17.6
years in gBRCA2 carriers and non-carriers, respectively (HR 2.12; p = 0.002), Median CSS in gBRCA2 carriers increased to 11.3 and 13.4 years in the absence of BRCA2-RB1 deletion or MYC amplification, respectively. Median CSS of non-carriers decreased to 8 and 2.6 years
if BRCA2-RB1 deletion or MYC amplification were detected.
Conclusions
gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.
Keywords
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Article info
Publication history
Published online: March 03, 2023
Accepted:
February 22,
2023
Received in revised form:
February 21,
2023
Received:
December 7,
2022
Identification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
