Identification and Characterization of New Alu Element Insertion in the BRCA1 Exon 14 Associated with Hereditary Breast and Ovarian Cancer

Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant cancer predisposition syndrome characterized by an increased risk of breast and ovarian cancers. Germline pathogenic variants in BRCA1 are found in about 7–10% of all familial breast cancers and 10% of ovarian cancers. Alu elements are the most abundant mobile DNA element in the human genome and are known to affect the human genome by different mechanisms leading to human disease. We report here the detection, by next-generation sequencing (NGS) analysis coupled with a suitable bioinformatics pipeline, of an AluYb8 element in exon 14 of the BRCA1 gene in a family with HBOC history first classified as BRCA-negative by Sanger sequencing and first NGS analysis. The c.4475_c.4476insAluYb8 mutation impacts splicing and induces the skipping of exon 14. As a result, the produced mRNA contains a premature stop, leading to the production of a short and likely non-functional protein (pAla1453Glyfs*10). Overall, our study allowed us to identify a novel pathogenic variant in BRCA1 and showed the importance of bioinformatics tool improvement and versioning.

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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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Case series: Breast and ovarian cancer syndrome

10.1055/s-0039-1685348 ◽

2016 ◽

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Brca Mutation ◽

Family Members ◽

Case Series ◽

Second Primary ◽

Time Interval ◽

Breast And Ovarian Cancer ◽

Ovarian Carcinomas ◽

Increased Risk

Aims and Objectives: To report a series of cases with breast and ovarian carcinomas either in same patient or in a family and identifying the importance of BRCA 1,2 genetic testing in such individuals. Materials and Methods: The medical records of breast and ovarian cancer patients operated over past 3 years at a single institute were reviewed retrospectively and their clinical profile, family history, final pathological reports and follow up data was collected. Results: 8 patients were found to have breast and ovarian malignancies, out of which 3 had synchronous breast and ovarian cancers, 4 had metachronous and 1 patient with ovarian cancer had history of breast cancer in family. Median age of presentation to the hospital was 47 years and median time interval in metachronous disease patients was 5.5 years. Conclusion: About 5% of people who have breast cancer and about 10% of women who have ovarian cancer have HBOC, caused by germline mutation in BRCA1, 2 gene. These individuals have increased risk of developing breast cancer at younger age, TNBC, or developing a second primary in breast or ovary plus an overall risk of breast/ovarian/prostate/pancreatic malignancies in other family members due to inheritable mutation. Identification of BRCA mutation in such individuals can help family members to undergo genetic counseling and follow different screening and prevention guidelines from general population thus reducing the cancer risks.

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Colorectal Cancer Risk in Women with Gynecologic Cancers—A Population Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10143127 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3127

Author(s):

Szu-Chia Liao ◽

Hong-Zen Yeh ◽

Chi-Sen Chang ◽

Wei-Chih Chen ◽

Chih-Hsin Muo ◽

...

Keyword(s):

Colorectal Cancer ◽

Ovarian Cancer ◽

Cervical Cancer ◽

Cohort Study ◽

Cancer Patients ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Gynecologic Cancer ◽

Ovarian Cancers ◽

Increased Risk

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.

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