Detection of germline mutations in the BRCA1 gene by RNA-based sequencing

2001 ◽  
Vol 18 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Anna Jakubowska ◽  
Bohdan Górski ◽  
Tomasz Byrski ◽  
Tomasz Huzarski ◽  
Jacek Gronwald ◽  
...  
Keyword(s):  
Brca1 Gene ◽  
Germline Mutations

scholarly journals High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area

2005 ◽  
Vol 7 (5) ◽  
Author(s):  
Petr Pohlreich ◽  
Michal Zikan ◽  
Jana Stribrna ◽  
Zdenek Kleibl ◽  
Marketa Janatova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Brca1 Gene ◽  
Germline Mutations ◽  
Breast And Ovarian Cancer

scholarly journals BRCA1 Gene Mutations in Sporadic Ovarian Carcinomas: Detection by PCR and Reverse Allele-specific Oligonucleotide Hybridization

1999 ◽  
Vol 45 (7) ◽  
pp. 976-981 ◽  
Author(s):  
Dan Tong ◽  
Margit Stimpfl ◽  
Alexander Reinthaller ◽  
Norbert Vavra ◽  
Silvia Müllauer-Ertl ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Detection System ◽  
Brca1 Mutation ◽  
Simultaneous Detection ◽  
Brca1 Gene ◽  
Germline Mutations ◽  
Ovarian Carcinomas ◽  
Primary Fallopian Tube Carcinoma ◽  
Oligonucleotide Hybridization ◽  
Allele Specific

Abstract Background: Although germline mutations in BRCA1 play a central role in familial breast and ovarian cancers, to date, no somatic mutations in BRCA1 have been reported in sporadic breast cancer, and only five somatic mutations have been identified in the sporadic ovarian carcinomas. Because loss of heterozygosity appears frequently at the BRCA1 locus in nonfamilial breast and ovarian carcinomas, we searched for mutations in the BRCA1 gene in sporadic ovarian tumors. Methods: We developed a detection system based on PCR and reverse allele-specific oligonucleotide hybridization on membrane strips for the simultaneous detection of 17 frequently occurring mutations in the BRCA1 gene. Results: As little as 2% mutant DNA in a sample could be detected. Two of 122 DNA samples isolated from sporadic ovarian tumor biopsies contained the Cys61Gly mutation. Both mutations were germline mutations. One of these was an ovarian metastasis of a primary fallopian tube carcinoma. The tubal carcinoma was also confirmed to contain the Cys61Gly mutation. Conclusions: This is the first report that a germline BRCA1 mutation is associated with primary tubal carcinoma. The 17 specific mutations in the BRCA1 gene do not play a major role in the tumorigenesis and progression of sporadic ovarian cancer.

scholarly journals GERMINAL MUTATIONS IN HOMOLOGOUS RECOMBINATION GENES IN A POPULATION OF PATIENTS WITH PANCREATIC CANCER: A SINGLE CENTRE EXPERIENCE

2018 ◽  
Vol 8 (3) ◽  
pp. 5-12
Author(s):  
I. A. Pokataev ◽  
A. S. Popova ◽  
I. S. Abramov ◽  
M. A. Emelyanova ◽  
Т. V. Nasedkina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Homologous Recombination ◽  
Germline Mutation ◽  
Brca1 Mutation ◽  
Brca1 Gene ◽  
Distant Metastases ◽  
Germline Mutations ◽  
Malignant Neoplasms ◽  
Brca1 Gene Mutation

Objective.To estimate the frequency of germline mutations in homologous recombination genes in a population of patients with pancreatic cancer and to assess the possibility to predict the risk of mutation carriage based on the clinical and anamnestic data.Materials and methods.The study included patients diagnosed with pancreatic cancer, blood samples of which were taken to detect clinically significant germline mutations in the BRCA1, BRCA2, CHEK2, BLM, NBS1, and PALB2 genes. Clinical data and family history data were collected for each patient.Results.The study included 99 patients. Mutations in BRCA1 gene were detected in 4 % of cases, in CHEK2 gene – in 2 %. No mutations were detected in the BRCA2, as in BLM, NBS1, and PALB2 genes. Localization of primary tumor, presence of distant metastases, stage of disease, family history of malignant neoplasms did not correlate with the risk of BRCA1 mutation (p>0.05). The patient’s eligibility for NCCN criteria for BRCA1 gene mutation diagnosis proved to be a significant marker of germline mutation presence (p=0.043).Conclusions.NCCN criteria for genetic testing are the best predictor of BRCA1 germline mutation in patients with pancreatic cancer.

scholarly journals Age-dependent penetrance of different germline mutations in the BRCA1 gene

2009 ◽  
Vol 62 (4) ◽  
pp. 350-356 ◽  
Author(s):  
F Al-Mulla ◽  
J M Bland ◽  
D Serratt ◽  
J Miller ◽  
C Chu ◽  
...  
Keyword(s):  
Brca1 Gene ◽  
Germline Mutations ◽  
Age Dependent

Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation

1995 ◽  
Vol 4 (10) ◽  
pp. 1953-1956 ◽  
Author(s):  
Mieko Matsushima ◽  
Kanji Kobayashi ◽  
Mitsuru Eml ◽  
Junko Saito ◽  
Kaoru Suzumori ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Somatic Mutation ◽  
Mutation Analysis ◽  
Brca1 Gene ◽  
Germline Mutations

scholarly journals Analysis of the BRCA1 gene coding regions in patients with luminal B breast cancer

2020 ◽  
pp. 22-23
Author(s):  
А.М. Певзнер ◽  
М.К. Ибрагимова ◽  
М.М. Цыганов
Keyword(s):  
Breast Cancer ◽  
Tumor Tissue ◽  
Brca1 Gene ◽  
Germline Mutations ◽  
Coding Region ◽  
Luminal B ◽  
Coding Regions ◽  
Disease Prognosis ◽  
Gene Coding ◽  
Low Expression

Наши предыдущие исследования показали, что дефицит гена BRCA1, вызванный изменениями в опухоли, такими как низкая экспрессия, делеция, потеря гетерозиготности, может быть связан с эффективностью химиотерапии и прогнозом заболевания. Однако даже при отсутствии этих факторов эффективность терапии таксотером была переменной. Это может быть связано с наличием других соматических изменениий гена BRCA1 в опухолевой ткани, и их определение поможет определить индивидуальную стратегию лечения для каждого пациента с раком молочной железы. Здесь мы исследовали весь спектр герминальных и соматических мутаций кодирующей области генов BRCA1/2 в опухолевой ткани. В целом, наши результаты показывают, что имеет смысл принимать во внимание не только выявленные герминальные мутации, но и соматические изменения в генах BRCA1/2 при назначении терапии. Our previous studies have shown that BRCA1 gene deficiency caused by changes in the tumor such as low expression, deletion, loss of heterozygosity, etc., can be associated with the effectiveness of chemotherapy and the disease prognosis. However, even in the absence of these factors, the effectiveness of taxotere therapy was variable. This may be due to the availability of another BRCA1 gene somatic changes in the tumor tissue and their determination will help to define the personalize treatment strategy for each breast cancer patient. Here we investigated the entire spectrum germline and somatic mutation of coding region of the BRCA1/2 gene in tumor tissue. Overall, our results suggest that it makes sense to take into account not only identified germline mutations, but also somatic changes in the BRCA1/2 gene when appointment taxotere

scholarly journals Germline mutations in the BRCA1 gene predisposing to breast and ovarian cancers in Upper Silesia population.

2002 ◽  
Vol 49 (2) ◽  
pp. 351-356 ◽  
Author(s):  
Ewa Grzybowska ◽  
Marzena Siemińska ◽  
Helena Zientek ◽  
Ewa Kalinowska ◽  
Jadwiga Michalska ◽  
...  
Keyword(s):  
Bilateral Breast Cancer ◽  
Brca1 Gene ◽  
Germline Mutations ◽  
Ovarian Cancers ◽  
Frequent Mutations ◽  
Allele Specific ◽  
Specific Amplification ◽  
185Delag Mutation ◽  
Healthy Persons ◽  
Pcr Test

Germline mutations in the BRCA1 or BRCA2 genes predispose their carriers to breast or/and ovary cancers during their lifetime. The most frequent mutations: 5382insC, 185delAG, C61G and 4153delA in BRCA1, and 6174delT and 9631delC in BRCA2 were studied in a group of 148 probands admitted for genetic counseling, using allele-specific amplification (ASA) PCR test. Fifteen carriers of three different mutations: 5382insC, 185delAG and C61G in BRCA1 were found. Two families carried the 185delAG mutation and additional two C61G in BRCA1. Nobody carried the mutation 4153delA in BRCA1 nor 6174delT or 9631delC in BRCA2. Most of the carriers of a germline mutation were observed among the patients who developed bilateral breast cancer (17%). The lowest frequency of the germline mutations was found in the healthy persons who had two or more relatives affected with breast or ovarian cancer.

Genotype and phenotype in hereditary and sporadic breast cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10538-10538
Author(s):  
G. Giorgetti ◽  
E. Galizia ◽  
F. Bianchi ◽  
C. Ferretti ◽  
F. Corradini ◽  
...  
Keyword(s):  
Cancer Susceptibility ◽  
Cpg Island ◽  
Direct Sequencing ◽  
Gene Expression Signature ◽  
Brca1 Gene ◽  
Promoter Hypermethylation ◽  
Germline Mutations ◽  
Breast Cancers ◽  
Brca1 Protein ◽  
Brca1 Promoter

10538 Background: BRCA1 protein is involved in distinct DNA-repair processes. Germline mutations in BRCA1 gene confer cancer susceptibility. A frequent mechanism for epigenetic inactivation is hypermethylation of the CpG island in promoters of tumours suppressor genes. BRCA1 promoter hypermethylation has been found in a variable percentage of breast cancers (15–30%). BRCA1-associated breast cancers are usually high-grade, poorly differentiated and stain negative for HER2/neu, oestrogen and progesterone receptors (ER, PgR). Many studies have shown that hereditary BRCA1 and basal-like sporadic breast tumours have a similar phenotype and gene expression signature. Methods: By clinical criteria, 223 patients were selected and, for each patient, the probability to carry a BRCA1 mutation was calculated using the software BRCAPRO and Manchester Score System. All patients were studied by direct sequencing and MLPA of BRCA1 Open Reading Frames (ORFs). Thirty sporadic breast carcinomas, from women undergone surgery for primary invasive breast carcinoma between 1995 and 2001, were selected on the basis of negative staining for ER, PgR and HER2/neu (“BRCA-like”). In these patients, Methylation Specific-PCR and Bisulfite Sequencing on genomic DNA (obtained from sections of paraffin-embedded tissues and modified with sodium bisulfite) were used to assess the methylation pattern of BRCA1 promoter. BRCA1 immunohystochemical analysis (IHC) was performed in all patients. Results: We identified 17 patients with deleterious germline mutations in BRCA1. In “BRCA-like” patients, 13 methylated and 17 unmethylated cases were found by methylation analysis of BRCA1 promoter. The BRCA1 IHC was performed in all available samples ( table 1 ). Conclusions: Hypermethylation of BRCA1 promoter was found in 43% of “BRCA- like” patients. Expression of BRCA1 seems to correlate with hypermethylation of its promoter. Further studies are in progress to better understand the possible role of BRCA1 promoter hypermethylation in sporadic breast cancers. [Table: see text] No significant financial relationships to disclose.

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