scholarly journals Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer

1998 ◽  
Vol 78 (6) ◽  
pp. 771-773 ◽  
Author(s):  
S Lehrer ◽  
F Fodor ◽  
RG Stock ◽  
NN Stone ◽  
C Eng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Brca2 Gene ◽  
Brca1 Gene ◽  
Ashkenazi Jewish ◽  
185Delag Mutation

scholarly journals Genetic architecture of prostate cancer in the Ashkenazi Jewish population

2011 ◽  
Vol 105 (6) ◽  
pp. 864-869 ◽  
Author(s):  
J Vijai ◽  
T Kirchhoff ◽  
D Gallagher ◽  
N Hamel ◽  
S Guha ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Jewish Population ◽  
Genetic Architecture ◽  
Ashkenazi Jewish ◽  
Ashkenazi Jewish Population

scholarly journals The Role of the BRCA2 Gene in Susceptibility to Prostate Cancer Revisited

2008 ◽  
Vol 17 (8) ◽  
pp. 1843-1848 ◽  
Author(s):  
Elaine A. Ostrander ◽  
Miriam S. Udler
Keyword(s):  
Prostate Cancer ◽  
Brca2 Gene

Screening of BRCA2 mutated men for detection of prostate cancer: Preliminary results from a national high volume cancer center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Monica Zuradelli ◽  
Nicolo' Buffi ◽  
Paolo Bianchi ◽  
Carla Barbara Ripamonti ◽  
Monica Barile ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Screening Program ◽  
Brca2 Mutation ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Brca2 Gene ◽  
Pathogenic Mutation ◽  
Genealogical Trees ◽  
Targeted Screening

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( > 4ng/ml and > 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.

scholarly journals Y chromosome haplogroups and prostate cancer in populations of European and Ashkenazi Jewish ancestry

2012 ◽  
Vol 131 (7) ◽  
pp. 1173-1185 ◽  
Author(s):  
Zhaoming Wang ◽  
Hemang Parikh ◽  
Jinping Jia ◽  
Timothy Myers ◽  
Meredith Yeager ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Y Chromosome ◽  
Ashkenazi Jewish ◽  
Jewish Ancestry

scholarly journals Somatic aberrations of BRCA1 gene are associated with progressive and stem cell-like phenotype of prostate cancer

2018 ◽  
Author(s):  
Aleksandra Omari ◽  
Paulina Nastały ◽  
Aneta Bałabas ◽  
Michalina Dąbrowska ◽  
Beata Bielińska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
Gleason Score ◽  
Gene Loss ◽  
Epithelial Mesenchymal Transition ◽  
Gene Dosage ◽  
Brca1 Gene ◽  
Ki 67 ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

AbstractBackgroundBRCA1 is a pivotal tumor suppressor. Its dysfunction is known to play a role in different tumor entities. Among others, BRCA1 germline mutations account for higher risk and more aggressive course of prostate cancer (PCa). In addition, somatic BRCA1 gene loss was demonstrated to be a signature of PCa dissemination to regional lymph nodes and peripheral blood, and indicate worse clinical outcome. In order to substantiate the data for BRCA1 gene loss in PCa and to reveal its phenotypical background, BRCA1 gene status was assessed in a large cohort of PCa patients and compared to different molecular factors.MethodsBRCA1 gene dosage was assessed in 2398 tumor samples from 1199 PCa patients using fluorescent in situ hybridization. It was compared to clinic-pathological parameters, patients’ outcome as well as selected proteins (Ki-67, apoptosis marker, cytokeratins, vimentin, E- and N-cadherin, ALDH1 and EGFR) examined by immunohistcohemistry.ResultsBRCA1 losses were found in 10%, whereas gains appeared in 7% of 603 informative PCa patients. BRCA1 losses correlated to higher T status (p=0.027), Gleason score (p=0.039), shorter time to biochemical recurrence in patients with Gleason score >7 independently of other factors (multivariate analysis, p=0.005) as well as expression of proteins regulating stemness and epithelial-mesenchymal transition i.e. ALDH1 (p=0.021) and EGFR (p=0.011), respectively. BRCA1 gains correlated to shorter time to metastasis (p=0.012) and expression of ALDH1 (p=0.014).ConclusionsThe presented results support the assumption that BRCA1 gene losses contribute to a progressive and stem cell-like phenotype of PCa. Furthermore, they reveal that also BRCA1 gain might mark more invasive tumors.

scholarly journals Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3223
Author(s):  
Verena Lieb ◽  
Amer Abdulrahman ◽  
Katrin Weigelt ◽  
Siegfried Hauch ◽  
Michael Gombert ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapy Monitoring ◽  
Brca1 Gene ◽  
Sequence Variants ◽  
Liquid Biopsies ◽  
Treatment Change ◽  
Cell Free Dna ◽  
Free Dna

Prostate cancer (PCa) is the second most common malignant cancer and is a major cause of morbidity and mortality among men worldwide. There is still an urgent need for biomarkers applicable for diagnosis, prognosis, therapy prediction, or therapy monitoring in PCa. Liquid biopsies, including cell-free DNA (cfDNA) and circulating tumor cells (CTCs), are a valuable source for studying such biomarkers and are minimally invasive. In our study, we investigated the cfDNA of 34 progressive PCa patients, via targeted sequencing, for sequence variants and for the occurrence of CTCs, with a focus on androgen receptor splice variant 7 (AR-V7)-positive CTCs. The cfDNA content was associated with overall survival (OS; p = 0.014), disease-specific survival (DSS; p = 0.004), and time to treatment change (TTC; p = 0.001). Moreover, when considering all sequence variants grouped by their functional impact and allele frequency, a significant association with TTC (p = 0.017) was observed. When investigating only pathogenic or likely pathogenic gene variants, variants of the BRCA1 gene (p = 0.029) and the AR ligand-binding domain (p = 0.050) were associated with a shorter TTC. Likewise, the presence of CTCs was associated with a shorter TTC (p = 0.031). The presence of AR-V7-positive CTCs was associated with TTC (p < 0.001) in Kaplan–Meier analysis. Interestingly, all patients with AR-V7-positive CTCs also carried TP53 point mutations. Altogether, analysis of cfDNA and CTCs can provide complementary information that may support temporal and targeted treatment decisions and may elucidate the optimal choice within the variety of therapy options for advanced PCa patients.

scholarly journals Analysis of variators in the brca1 and brca2 genes by ngs in patients from central brazil with suspected hboc syndrome: a new pathogenic variant identified

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Rebeca Mota Goveia ◽  
Paula Francinete Faustino da Silva ◽  
Thais Bomfim Teixeira ◽  
Ruffo de Freitas ◽  
Elisângela de Paula Silveira Lacerda
Keyword(s):  
At Risk ◽  
In Silico ◽  
Brca2 Gene ◽  
Brca1 Gene ◽  
Published Data ◽  
Brca1 And Brca2 ◽  
Pathogenic Potential ◽  
Pathogenic Variants ◽  
Brca1 And Brca2 Genes ◽  
Patients At Risk

About 10‒15% of breast cancer cases are due to deleterious germ changes, more than half of which are located in the BRCA1 or BRCA2 genes. The screening of variants in these genes for patients at risk brings benefits for better clinical management of the patient as well as for the prevention of disease recurrences both in the proband and in their relatives. The profile of genetic variants is little known to the Brazilian population and, to date, there are no published data for the population of the central region of the country. This study aimed to analyze the profile of pathogenic variants (VP) and of uncertain significance (VUS) in the BRCA1 and BRCA2 genes in this population. We selected 102 patients seen at Hospital das Clínicas, Universidade Federal de Goiás, with clinical diagnosis of invasive ductal carcinoma that met the criteria of the National Comprehensive Cancer Networking 2016/2 for hereditary breast and ovarian cancer syndrome. A collection of 4mL of peripheral blood was carried out and submitted to subsequent extraction of genomic DNA, carried out using the PureLink kit (Invitrogen). The genes in question had all their exon-intron regions sequenced using the MiSeq device (Illumina) and the raw data were evaluated using the Sophia DDM software. The risk of in silico pathogenicity of the VUS was analyzed by the software POLYPHEN2, MutationTaster, SIFT, ESP5400, G1000, GnomAD. Of the total of 102 patients evaluated in this study, 22 (21.56%) had PV or VUS in the BRCA1 or BRCA2 genes. Of these, 16 patients (72.81%) had pathogenic variants, eight with PV in BRCA1 (c.5266dupC (2), c.3331_3334delCAAC, c.211A>G, c.3228_3229delAG, c.3700_3704delGTAAA, c.4484G>T and c.5305_5306ins20) and eight with PV in BRCA2 (c.156_157insAlu, c.4829_4830delTG, c.8488-1G>A, c.6405_6409delCTTAA (3), c.517-1G>A, c.2808_2811delACAA). A total of 7 patients (31.8%) presented VUS in these genes, one in the BRCA1 gene (c.179A>G) and five in the BRCA2 gene (c.280C>T, c.811G>A, 1096T>G, 1441A>G and c.5270A>G) of which only the variant c.1441A>G had low pathogenic potential in silico. A new PV still not described in the literature was also identified, variant c.5305_5306ins20 in the BRCA1 gene. These data suggest that all patients at risk in this population should be evaluated for PV or VUS in the BRCA1 and BRCA2 genes since the presence of these variants can help in the patient's prognosis and disease prevention.

scholarly journals Common Variation in the BRCA1 Gene and Prostate Cancer Risk

2007 ◽  
Vol 16 (7) ◽  
pp. 1510-1516 ◽  
Author(s):  
J. A. Douglas ◽  
A. M. Levin ◽  
K. A. Zuhlke ◽  
A. M. Ray ◽  
G. R. Johnson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Brca1 Gene ◽  
Common Variation
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