Dataset Information

Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.

ABSTRACT:

Background

Germline mutations in BRCA2 have been linked to a higher risk of prostate cancer (PCa), and high frequency of BRCA1 and BRCA2 (BRCA1/2) gene alterations was recently reported in metastatic castration-resistant PCa specimens. Mutations in BRCA2 vary in racial and ethnic groups including African-American (AA) and Caucasian-American (CA) populations.

Methods

BRCA1 and BRCA2 genes were sequenced (Ion AmpliSeq targeted sequencing) in archived blood DNA specimens in 1240 PCa patients, including 30% AA patients, in three different cohorts: localized early stage (T2) PCa (N?=?935); advanced PCa (50% T3-4) (N?=?189); and metastatic PCa (N?=?116). The sequences were analyzed for known and novel mutations in BRCA1/2. Statistical analyses were performed to determine associations of the mutations with clinico-pathological parameters.

Results

BRCA2 mutations with known pathogenic annotation were significantly more prevalent in men with advanced and metastatic PCa (3.1%) compared to patients with an organ-confined disease (0.7%). AA patients carried more frequently BRCA1/2 variants of unknown significance (VUS) when compared to Caucasian Americans (4.6 vs. 1.6%, respectively). Significantly, pathogenic BRCA2 mutations in men with localized early stage PCa increased the risk of distant metastasis.

Conclusions

Germline variants of unknown significance in BRCA1/2 are more frequent in AA than CA PCa patients; however, the prevalence of pathogenic mutations were similar across the races. Patients carrying BRCA2 pathogenic mutations are more likely to progress to metastasis.

SUBMITTER: Petrovics G

PROVIDER: S-EPMC6760554 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.

Petrovics Gyorgy G Price Douglas K DK Lou Hong H Chen Yongmei Y Garland Lisa L Bass Sara S Jones Kristine K Kohaar Indu I Ali Amina A Ravindranath Lakshmi L Young Denise D Cullen Jennifer J Dorsey Tiffany H TH Sesterhenn Isabell A IA Brassell Stephen A SA Rosner Inger L IL Ross Doug D Dahut William W Ambs Stefan S Figg William Douglas WD Srivastava Shiv S Dean Michael M

Prostate cancer and prostatic diseases 20181212 3

<h4>Background</h4>Germline mutations in BRCA2 have been linked to a higher risk of prostate cancer (PCa), and high frequency of BRCA1 and BRCA2 (BRCA1/2) gene alterations was recently reported in metastatic castration-resistant PCa specimens. Mutations in BRCA2 vary in racial and ethnic groups including African-American (AA) and Caucasian-American (CA) populations.<h4>Methods</h4>BRCA1 and BRCA2 genes were sequenced (Ion AmpliSeq targeted sequencing) in archived blood DNA specimens in 1240 PCa ...[more]

PMID: 30542053

Similar Datasets

Project description:Aim of workReporting the incidence and the variants of BRCA1/2 mutations in ovarian cancer patients exploring their effects on the treatment outcomes.Patients and methodsIn total, 104 patients with epithelial ovarian cancer were prospectively recruited to the study. Analysis consisted of the sequencing of all the translated exons and immediately adjacent intronic regions of the BRCA1/2 genes. Responses to multiple lines of chemotherapy were assessed, as well as the effect of BRCA gene mutations on progression-free survival (PFS) and overall survival (OS).ResultsPathogenic BRCA1/2 mutations were found in 21.15% of the patients. BRCA1 mutations represented 68.2% of the total mutations. Two novel BRCA1 mutations were identified. Age at diagnosis was a strong predictor of the presence of a pathogenic BRCA1/2 mutation. Patients with a family history of cancer had a higher incidence of BRCA mutations (P=0.005). As high as 72% of the patients with BRCA mutations were diagnosed at advanced stage. High-grade serous tumors have a higher incidence of pathogenic mutation (P=0.07). Response to neoadjuvant chemotherapy was high (93.9%). All patients underwent surgery which was optimal in 73.1% of the patients. As high as 85.6% of the patients received adjuvant chemotherapy. Relapse rate was 45.2%. Visceral metastasis was more often in BRCA carriers (P=0.01). Patients carrying pathogenic BRCA1/2 mutations had a longer median PFS of 42.43 months (95% CI 32.04-52.83) compared to 22.24 months (95% CI 14.83-29.58) for non-carriers (P=0.08). OS was 64.32 months (95% CI 38.09-90.06) for BRCA mutation patients versus 56.63 months (95% CI 50.05-63.21) (P=0.04) for non-carriers. In multivariate analysis, early stage at diagnosis and optimal debulking were the only independent predictors of better PFS and OS.ConclusionWe documented a number of pathogenic BRCA1 and 2 mutations in this patients cohort; two novel mutations were detected. BRCA status seemed to affect survival in ovarian cancer patients.

Dataset Information

Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.

Background

Methods

Results

Conclusions

Publications

Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets