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

被引：3

作者：

Lozano, Rebeca ^{[1
,2
]}

Castro, Elena ^{[1
,3
,28
]}

-Campos, Fernando Lopez ^{[4
]}

Thorne, Heather ^{[5
]}

Ramirez-Backhaus, Miguel ^{[6
]}

Aragon, Isabel M. ^{[1
]}

Cendon-Florez, Ylenia ^{[1
]}

Gutierrez-Pecharroman, Ana ^{[1
,7
]}

Salles, Daniela C. ^{[8
]}

Romero-Laorden, Nuria ^{[9
]}

Lorente, David ^{[10
]}

Gonzalez-Peramato, Pilar ^{[11
]}

Calatrava, Ana ^{[12
]}

Alonso, Concepcion ^{[13
]}

Anido, Urbano ^{[14
]}

Arevalo-Lobera, Sara ^{[15
]}

Balmana, Judith ^{[16
,17
]}

Chirivella, Isabel ^{[18
]}

Juan-Fita, Maria Jose ^{[19
]}

Llort, Gemma ^{[20
]}

Cajal, Teresa Ramon Y. ^{[21
]}

Almagro, Elena ^{[22
]}

Alameda, Daniel ^{[1
]}

Lopez-Casas, Pedro P. ^{[23
]}

Herrera, Bernardo ^{[1
,24
]}

Mateo, Joaquin ^{[16
,17
]}

Pritchard, Colin C. ^{[25
]}

Antonarakis, Emmanuel S. ^{[26
]}

Lotan, Tamara L. ^{[8
]}

Rubio-Briones, Jose ^{[6
]}

Sandhu, Shahneen ^{[27
]}

Olmos, David ^{[23
]}

机构：

[1] Inst Invest Biomed Malaga IBIMA, Genitourinary Canc Translat Res Unit, Malaga, Spain

[2] Hosp Univ Salamanca, Dept Med Oncol, Salamanca, Spain

[3] Hosp Univ 12 Octubre, Translat Canc Genet Grp, Madrid, Spain

[4] Hosp Univ Ramon y Cajal, Dept Radiat Oncol, Madrid, Spain

[5] Peter MacCallum Canc Ctr, kConFab, Melbourne, Australia

[6] Fdn Inst Valenciano Oncol, Urol Dept, Valencia, Spain

[7] Hosp Getafe, Dept Pathol, Getafe, Spain

[8] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD USA

[9] Hosp Univ La Princesa, Med Oncol Dept, Madrid, Spain

[10] Hosp Prov Castellon, Med Oncol Dept, Castellon De La Plana, Spain

[11] Univ Autonoma Madrid, Hosp Univ La Paz, Pathol Dept, Madrid, Spain

[12] Fdn Inst Valenciano Oncol, Pathol Dept, Valencia, Spain

[13] Hosp Univ La Princesa, Genet Dept, Madrid, Spain

[14] Hosp Clin Univ Santiago, Med Oncol Dept, Santiago De Compostela, Spain

[15] Hosp Univ Donostia, Med Oncol Dept, Donostia San Sebastian, Spain

[16] Vall dHebron Inst Oncol VHIO, Barcelona, Spain

[17] Vall dHebron Univ Hosp, Barcelona, Spain

[18] Hosp Clin Univ Valencia, Med Oncol Dept, Valencia, Spain

[19] Fdn Inst Valenciano Oncol, Med Oncol Dept, Valencia, Spain

[20] Parc Tauli Hosp Univ, Med Oncol Dept, Sabadell, Spain

[21] Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain

[22] Hosp Univ Quiron, Med Oncol Dept, Madrid, Spain

[23] Hosp Univ Octubre 12, Inst Invest Sanitaria 12 Octubre Imas12, Med Oncol Dept, Genom & Therapeut Prostate Canc Grp, Madrid, Spain

[24] Hosp Univ Virgen de la Victoria, Urol Dept, Malaga, Spain

[25] Univ Washington, Dept Lab Med & Pathol, Seattle, WA USA

[26] Johns Hopkins Univ, Dept Med Oncol, Sch Med, Baltimore, MD USA

[27] Univ Melbourne, Sir Peter Maallum Dept Oncol, Parkville, Vic, Australia

[28] Hosp Univ 12 Octubre, Dept Med Oncol, Av Cordoba S-N, Madrid 28041, Spain

来源：

EUROPEAN JOURNAL OF CANCER | 2023年 / 185卷

关键词：

Prostate cancer; Germline; BRCA2; Survival outcomes; Disease progression; C-MYC; BRCA2; AMPLIFICATION; ASSOCIATION; CRIBRIFORM; PATHOLOGY; SURVIVAL;

D O I：

10.1016/j.ejca.2023.02.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 cor-related 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 amplifi-cation (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 in-creased 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.& COPY; 2023 Elsevier Ltd. All rights reserved.

引用

页码：105 / 118

页数：14

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