scholarly journals Identifying a BRCA2 c.5722_5723del mutation in a Han-Chinese family with breast cancer

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Yi Guo ◽  
Peng Wang ◽  
Xiaorong Li ◽  
Shaihong Zhu ◽  
Hongbo Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Risk Estimation ◽  
Susceptibility Genes ◽  
Han Chinese ◽  
Chinese Family ◽  
Dna Double Strand Breaks ◽  
Whole Exome ◽  
Exon 11 ◽  
Brca1 Brca2

Abstract Breast cancer (BC) is the most common female cancer found worldwide. It is responsible for 25% of all cancer patients in females. Hereditary BC accounts for about 5–10% of all BC cases. The breast cancer 1 gene (BRCA1) and the breast cancer 2 gene (BRCA2) are the two most-studied BC susceptibility genes. Genetic testing for disease-causing mutations in BRCA1, BRCA2, and other BC susceptibility genes is strongly recommended for members of families having a BC family history. The present study found a heterozygous c.5722_5723del mutation in the BRCA2 exon 11 of a large Han-Chinese BC family using whole exome sequencing and Sanger sequencing. It may cause DNA double-strand breaks repair dysfunction by disturbing homologous recombination, further resulting in BC. The study findings may help supplement and further improve genetic testing strategies and BC risk estimation methodologies in China.

Changing practice: moving to a specialist nurse-led service for BRCA gene testing

2020 ◽  
Vol 29 (10) ◽  
pp. S6-S13
Author(s):  
Nicola Scott ◽  
Jackie O'Sullivan ◽  
Kristjan Asgeirsson ◽  
Douglas Macmillan ◽  
Emma Wilson
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Cancer Genetics ◽  
Waiting Times ◽  
Brca2 Gene ◽  
Individual Treatment ◽  
Clinical Genetics ◽  
Specialist Nurse ◽  
Gene Testing ◽  
Brca1 Brca2

Some 5–10% of all breast cancers are associated with a pathogenic variant in a breast cancer-associated gene (BRCA1/BRCA2). Historically, with referral to the Nottingham University Hospitals NHS Trust's clinical genetics department for genetic testing, waiting times were on average 12–14 weeks for an initial appointment and 4–6 months to obtain results from the date of testing. A specialist, nurse-led mainstreaming cancer genetics (MCG) service was set up in the trust's Nottingham Breast Institute (NBI) to: reduce waiting times for the initial consultation, counselling, consent and obtaining results for BRCA1/BRCA2 gene testing; and to ensure appropriate patients with breast cancer were offered genetic testing. Two breast clinical nurse specialists were trained so they could counsel, consent and give results for the BRCA1/BRCA2 gene testing directly to patients. Average waiting times for results from the time of testing were reduced to 35.8 days under the nurse-led service, which enabled oncologists and patients to consider individual treatment options at an earlier time. The MCG service reduced waiting times, resulting in an improved, more streamlined service for patients undergoing genetic testing. The MCG service extended the scope of practice of the breast nurse clinical specialists, embedded an expert advanced nursing role in the breast multidisciplinary team and developed nurse mentoring opportunities.

Breast cancer treatment according to pathogenic variants in cancer susceptibility genes in a population-based cohort.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
Allison W. Kurian ◽  
Kevin C. Ward ◽  
Paul Abrahamse ◽  
Ann S Hamilton ◽  
Dennis Deapen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Genetic Test ◽  
Cancer Susceptibility ◽  
Population Based ◽  
Susceptibility Genes ◽  
Breast Cancer Treatment ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
To Receive

560 Background: Increasing use of germline genetic testing may have unintended consequences on breast cancer treatment. We do not know whether treatment deviates from guidelines for women with pathogenic variants (PV) in cancer susceptibility genes. Methods: SEER data for all women aged ≥20 years, diagnosed with breast cancer in 2014-15 and reported to Georgia and California registries (N = 77,588) by December 1, 2016 were linked to germline genetic testing results from 4 laboratories that did nearly all clinical testing. We examined first course of therapy (before recurrence or progression) of stage < IV patients who linked to a genetic test: bilateral mastectomy (BLM) in candidates for surgery (unilateral, stages 0-III); post-lumpectomy radiation in those with an indication (all but age ≥70, stage I, hormone receptor (HR)-positive and HER2-negative); and chemotherapy in those without a definitive indication (stage I-II, HR-positive, HER2-negative and 21-gene recurrence score < 30). We report the percent treated based on multivariable modeling, adjusted for age, race, stage, grade, insurance and socioeconomic status. Results: The table shows that 9% of patients who linked to a genetic test result had a PV (N = 1,283). Compared to women with negative results,women with BRCA1/2 PVs were more likely to receive BLM, more likely to receive chemotherapy without definitive indication, and less likely to receive indicated radiation in their first course of therapy. Lower-magnitude effects were seen with other PVs but not variants of uncertain significance (VUS). Conclusions: In a population-based setting, women with PVs in BRCA1/2 or other cancer susceptibility genes may have a higher risk of receiving locoregional and systemic treatment that does not follow guidelines. [Table: see text]

Prevalence of BRCA1/2 pathogenic variants in triple negative breast cancer patients stratified according to age at diagnosis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13677-e13677
Author(s):  
Ana Blatnik ◽  
Marta Banjac ◽  
Ksenija Strojnik ◽  
Simona Hotujec ◽  
Vida Stegel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Age At Diagnosis ◽  
Breast Cancer Patients ◽  
Detection Rates ◽  
Mutational Spectrum ◽  
Pathogenic Variants ◽  
Brca1 Brca2

e13677 Background: Triple negative breast cancer (TNBC) is strongly associated with germline BRCA1 pathogenic/likely pathogenic variants (PV/LPVs), with up to 28% TNBC patients being BRCA1 PV/LPV carriers. More recently, PALB2 variants have also been shown to be associated with TNBC. Genetic testing in Slovenian hereditary breast and ovarian cancer (HBOC) patients yields consistently high BRCA1/2 detection rates. Four BRCA1 PVs are particularly common, suggesting possible founder effects. Our aim was to analyze the results of panel based genetic testing in Slovenian TNBC patients, with an emphasis on BRCA1/BRCA2 mutational spectrum and detection rates depending on age at diagnosis. Methods: We evaluated the results of genetic testing, performed using a multi-gene panel in 1000 consecutive breast cancer cases. Only 210 patients with TNBC were included in further analysis. We analyzed the mutational spectrum and BRCA1/2 detection rates in TNBC patients stratified according to age at diagnosis. Results: In 80/210 (38.1%) TNBC patients PV/LPVs in BRCA1/2 were identified. Of these, the majority (74/80) were BRCA1-positive. The following variants: c.181T > G, c.5266dupC, c.1687C > T, and c.844_850dupTCATTAC were identified in 64.4% of BRCA1 carriers. BRCA1/2 detection rate decreased with age at diagnosis but was still 18.2% after age 60 (for BRCA1/2 detection rates stratified according to age at diagnosis see table). In 12/210 (5.7%) TNBC patients PV/LPVs in three other genes were identified (3.3% PALB2, 1.4% CHEK2, and 1% ATM). Conclusions: Prevalence of PVs in BRCA1 appears very high in Slovenian TNBC patients and warrants further population-based allele frequency studies with implications for future population screening. High rates of BRCA1/BRCA2 PVs in patients older than 60 years at diagnosis justify testing all TNBC patients, especially in view of treatment options which now include PARP inhibitors. PALB2 was the second most commonly mutated gene in our patients. [Table: see text]

scholarly journals Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Qin Xiang ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Yi Guo ◽  
Zhijian Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Retinal Pigment ◽  
Han Chinese ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Stargardt Disease ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Stargardt disease (STGD1, OMIM 248200) is a common hereditary juvenile or early adult onset macular degeneration. It ultimately leads to progressive central vision loss. Here, we sought to identify gene mutations associated with STGD1 in a three-generation Han Chinese pedigree by whole exome sequencing and Sanger sequencing. Two novel potentially pathogenic variants in a compound heterozygous state, c.3607G>T (p.(Gly1203Trp)) and c.6722T>C (p.(Leu2241Pro)), in the ATP binding cassette subfamily A member 4 gene (ABCA4) were identified as contributing to the family’s STGD1 phenotype. These variants may impact the ABCA4 protein structure and reduce the retinal-activated ATPase activity, leading to abnormal all-trans retinal accumulation in photoreceptor outer segments and in retinal pigment epithelium cells. The present study broadens the mutational spectrum of the ABCA4 responsible for STGD1. A combination of whole exome sequencing and Sanger sequencing is likely to be a time-saving and cost-efficient approach to screen pathogenic variants in genetic disorders caused by sizable genes, as well as avoiding misdiagnosis. These results perhaps refine genetic counseling and ABCA4-targetted treatments for families affected by STGD1.

BRCAPRO Validation, Sensitivity of Genetic Testing of BRCA1/BRCA2, and Prevalence of Other Breast Cancer Susceptibility Genes

2002 ◽  
Vol 20 (11) ◽  
pp. 2701-2712 ◽  
Author(s):  
Donald A. Berry ◽  
Edwin S. Iversen ◽  
Daniel F. Gudbjartsson ◽  
Elaine H. Hiller ◽  
Judy E. Garber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Susceptibility Genes

PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.

scholarly journals A Comprehensive Screening Strategy of Breast Cancer Based on Different Penetrance Susceptibility Genes in Healthy Han Chinese Females

2021 ◽  
Author(s):  
Ling Hu ◽  
Chengbi Wu ◽  
Ping Liu ◽  
Lanbin Jiang ◽  
Yuntao Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Screening Method ◽  
Susceptibility Genes ◽  
Screening Strategy ◽  
Han Chinese ◽  
Polygenic Risk Score ◽  
The West ◽  
Genetic Determination ◽  
Polygenic Risk

Abstract Background: Morbidity and mortality associated with breast cancer (BC) had increased rapidly in China. Early screening and intervention could greatly reduce the risk of hereditary BC. Several risk models had been utilized over the last decades to predict individual BC risk, but most of them didn’t assess the polygenic risk of low-penetrant genes. A novel screening method integrating different penetrance susceptibility genes was eagerly needed.Methods: Twenty-three variants of high and moderate penetrance susceptibility genes (HVs) and twenty loci of low penetrance susceptibility genes (LVs) were selected from previous studies. Genotyping of these mutations were conducted among 3777 healthy Han Chinese women (HCW) and 401 BC subjects. Based on the mutation profiles, we raised a comprehensive screening strategy using HVs and LVs to evaluate the polygenic risk score (PRS) in healthy individuals.Results: Three HVs in BRCA1, BRCA2 and PALB2 genes mutated in the study population, which suggests the necessity of applying genetic determination to healthy HCW. LVs were widely carried in objects and their frequencies differed greatly between HCW and the west population. After quality control and lasso dimension reduction, nineteen of twenty-three LVs were involved to construct a logistic regression model to evaluate the cumulative genetic risk score. The area under curve (AUC), sensitivity and specificity of the model is 0.993, 0.9676 and 0.9617 respectively, indicating that it is robust. Finally, a screening strategy using HVs and LVs was put forward to evaluate the risk of BC in normal objects.Conclusion: The distribution of HVs and LVs differed greatly between Han Chinese females and the west population. A screening strategy combining HVs and LVs showed strong efficacy in distinguishing high risk individuals from healthy women.Trial registration: ChiCTR, ChiCTR2000038558. Registered 24 September 2020 - Retrospectively 37 registered, http://www.chictr.org.cn/showproj.aspx?proj=60543

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