Ovarian Cancer With Breast Metastasis and Two Pathogenic Variants of BRCA1 Gene

New Germinal Mutation of BRCA1 gene (c.829_832delAATA) in a Polish Patient with Breast/Ovarian Cancer

10.21203/rs.3.rs-126547/v1 ◽

2020 ◽

Author(s):

Malgorzata Ostrowska ◽

Justyna Podlodowska ◽

Jadwiga Sierocinska-Sawa ◽

Jacek Wojcierowski

Keyword(s):

Ovarian Cancer ◽

Brca1 Gene ◽

Adenosine Diphosphate ◽

Molecular Techniques ◽

Polish Population ◽

Single Nucleotide Variants ◽

Familial Predisposition ◽

Pathogenic Variants ◽

Therapeutic Benefits

Abstract Background: Determination of the BRCA1/BRCA2 mutation status in patients with breast and/or ovarian cancer is commonly performed using various molecular techniques. The use only of targeted PCR-based tests may not be sufficient, as not all possible variants are investigated. Quick and effective diagnosis in order to apply the appropriate treatment is extremely important. In the following study, we used next generation sequencing (NGS) techniques to identify novel pathogenic variants in BRCA1 and BRCA2. Methods: In this study, material (blood and FFPE) collected from a 67-year-old patient with ovarian cancer was used. The presence of hereditary mutations characteristic for the Polish population was examined using Sanger sequencing. BRCA1 and BRCA2 gene exons were amplified using the Devyser BRCA kit and sequenced on the Miniseq.Results: No germline mutations characteristic for the Polish population were detected. However,12 single nucleotide variants and 2 indels were identified. We found a new deleterious mutation of gene BRCA1 (c.829_832delAATA). To our knowledge, this mutation has not been reported yet in the Polish population and others. Conclusions: The use of the NGS technique increases the possibilities of detecting mutational changes in patients with ovarian and/or breast cancer. The frequency of somatic mutations in ovarian tumors is low (3% - 9%) but their detection may have therapeutic benefits due to the use of poly(adenosine diphosphate)-ribose polymerase (PARP) inhibitors. Quick determination of pathogenic variants is important to facilitate specific therapy in addition to the identification of familial predisposition to cancer.

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Spectrum of Germline Pathogenic Variants in BRCA1/2 Genes in the Apulian Southern Italy Population: Geographic Distribution and Evidence for Targeted Genetic Testing

Cancers ◽

10.3390/cancers13184714 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4714

Author(s):

Margherita Patruno ◽

Simona De Summa ◽

Nicoletta Resta ◽

Mariapia Caputo ◽

Silvia Costanzo ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Geographic Distribution ◽

Southern Italy ◽

Brca1 Gene ◽

Breast And Ovarian Cancer ◽

Pathogenic Variants ◽

Testing Strategies ◽

Brca1 Brca2 ◽

Over Time

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.

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BRCA1 and BRCA2 Testing through Next Generation Sequencing in a Small Cohort of Italian Breast/Ovarian Cancer Patients: Novel Pathogenic and Unknown Clinical Significance Variants

International Journal of Molecular Sciences ◽

10.3390/ijms20143442 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3442 ◽

Cited By ~ 3

Author(s):

Paola Concolino ◽

Gianfranco Gelli ◽

Roberta Rizza ◽

Alessandra Costella ◽

Giovanni Scambia ◽

...

Keyword(s):

Ovarian Cancer ◽

Next Generation Sequencing ◽

Brca2 Gene ◽

Brca1 Gene ◽

Prediction Algorithm ◽

Sequencing Analysis ◽

Next Generation ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Generation Sequencing

The aim of this report is to describe results of BRCA1 and BRCA2 Next Generation Sequencing Analysis (NGS) analysis in 132 selected Italian patients with breast/ovarian cancer. A NGS pipeline with a reliable Copy Number Variation (CNV) prediction algorithm was applied. In addition, VarSome and Priors V2.0 Software were employed for in silico analysis of novel missense variants. A total of 37 BRCA1 and BRCA2 pathogenic variants were found in 34 unrelated subjects with a frequency of positive patients of 25.7% (34/132). Twenty-four deleterious variants were detected in BRCA1 (representing the 64.9% of all identified pathogenic defects) and thirteen (35.1% of all identified pathogenic variants) in BRCA2 gene. The percentage of patients carrying a variant of unknown significance (VUS) was 7.5% (10/132). In addition, seven novel variants (five in BRCA2 and two in BRCA1 gene), never previously reported, were identified. Our approach represents a robust and easy-to-use method for full BRCA1/2 screening. However, a consistent number of our high-risk families still remained without a satisfying answer. Necessarily, further collective efforts must be directed to a definitive classification of VUSs. The future auspice is that the use of multi-gene panel and more advanced screenings, such as whole exome sequencing and/or RNA seq, in routine diagnostics increases the detection rate.

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A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

International Journal of Molecular Sciences ◽

10.3390/ijms22020889 ◽

2021 ◽

Vol 22 (2) ◽

pp. 889

Author(s):

Ava Kwong ◽

Cecilia Y. S. Ho ◽

Vivian Y. Shin ◽

Chun Hang Au ◽

Tsun Leung Chan ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Brca1 Gene ◽

Pathogenic Mutation ◽

Compound Heterozygous ◽

Strong Family History ◽

Breast And Ovarian Cancer ◽

Pathogenic Mutations ◽

Increased Risk ◽

History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

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Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽

10.3390/diagnostics11030547 ◽

2021 ◽

Vol 11 (3) ◽

pp. 547

Author(s):

Iolia Akaev ◽

Siavash Rahimi ◽

Olubukola Onifade ◽

Francis John Edward Gardner ◽

David Castells-Rufas ◽

...

Keyword(s):

Ovarian Cancer ◽

Unknown Origin ◽

Parp Inhibitors ◽

Serous Carcinoma ◽

High Grade ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Epithelial Cancers ◽

Pathogenic Variants ◽

Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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Long-Term Follow-Up of a Female Patient Treated with Olaparib—Hope for a Long Life without Relapse?

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073430 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3430

Author(s):

Mateusz Kozłowski ◽

Katarzyna Nowak ◽

Aneta Cymbaluk-Płoska

Keyword(s):

Ovarian Cancer ◽

Parp Inhibitor ◽

Brca1 Gene ◽

High Specificity ◽

Reproductive Organs ◽

Platinum Based Chemotherapy ◽

Long Term Follow Up ◽

History Of ◽

Advanced Stages

Ovarian cancer is one of the most common cancers of the reproductive organs. As there are no symptoms in the early stages, it is mainly detected in the advanced stages. Even then, the symptoms are non-specific and include, for example, abdominal pain, early satiety, or changes in bowel habits. Both biochemical marker levels and imaging studies are used in the initial diagnosis. However, it should be emphasized that they are not characterized by high specificity. Treatment is multistage, and usually first-line debulking surgery is used followed by platinum-based chemotherapy. Here we present a clinical case of a 56-year-old female, a carrier of a mutation in the BRCA1 gene, with a history of breast cancer and with recurrent epithelial ovarian cancer. The patient was qualified for treatment with a PARP inhibitor and is currently undergoing treatment with olaparib. In the patient’s follow up of 50 months to date, there has been no recurrence of cancer. Few side effects have been observed, and the most serious one that can be effectively treated is anemia. On the basis of the described case, the authors concluded that olaparib treatment is effective, relatively safe, and does not significantly affect daily functioning.

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