scholarly journals Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among high-risk Chinese individuals

2019 ◽  
Author(s):  
Di Shao ◽  
Shaomin Cheng ◽  
Fengming Guo ◽  
Yuying Yuan ◽  
Kunling Hu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Assessment ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Deleterious Mutations ◽  
Breast And Ovarian Cancer ◽  
Full Cohort ◽  
Cancer Susceptibility Genes ◽  
Multigene Panel

AbstractTo determine the prevalence and clinical prediction factors associated with deleterious mutations among 882 high-risk Chinese individuals who underwent multigene panel testing for hereditary breast and ovarian cancer (HBOC) risk assessment. Subjects were selected from individuals referred for genetic testing using a 21-gene panel (Oseq-BRCA) between January 2015 and March 2018. The distribution and prevalence of deleterious mutations were analyzed for the full cohort as well as subtypes. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) individuals. Of these, 26 mutations are not reported in public databases and literatures. In the ovarian cancer only subgroup, 115 deleterious mutations were identified in 429 patients (48.6%). Patients with ovarian cancer with mutations were enriched for a family history of breast or ovarian cancers (p < 0.05). In the breast cancer only subgroup, 31 deleterious mutations were identified in 261 patients. Most mutations occurred inBRCA1(8; 25.8%) andBRCA2(11; 35.5%). An additional 12 deleterious mutations (38.7%) were found in 7 other susceptibility genes. An increased frequency of mutation rate (57.9%) was observed in the subgroup of subjects with histories of both breast and ovarian cancer. Taken together, 19.50% of individuals carried a deleterious mutation in HBOC susceptibility genes in our cohort. Subgroup of subjects with histories of both breast and ovarian cancer had the highest prevalence of mutations. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of multigene panel in performing risk assessment.

scholarly journals Corrigendum to: Heterogeneity of germline variants in high risk breast and ovarian cancer susceptibility genes in India

2018 ◽  
Vol 1 (3) ◽  
pp. 134-134
Author(s):  
Archana Sharma-Oates ◽  
Abeer M Shaaban ◽  
Ian Tomlinson ◽  
Luke Wynne ◽  
Jean-Baptiste Cazier ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Breast And Ovarian Cancer ◽  
Germline Variants ◽  
Cancer Susceptibility Genes ◽  
High Risk Breast

scholarly journals Heterogeneity of germline variants in high risk breast and ovarian cancer susceptibility genes in India

2018 ◽  
Vol 1 (2) ◽  
pp. 75-87 ◽  
Author(s):  
Archana Sharma-Oates ◽  
Abeer M Shaaban ◽  
Ian Tomlinson ◽  
Luke Wynne ◽  
Jean-Baptiste Cazier ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Breast And Ovarian Cancer ◽  
Germline Variants ◽  
Cancer Susceptibility Genes ◽  
High Risk Breast

Value of multigene panel retesting of families with BRCA1/2 mutation-negative hereditary breast and ovarian cancer (HBOC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1582-1582
Author(s):  
Ekaterina Meshoulam Nikolaeva ◽  
Raul Terés ◽  
Daniela Camacho ◽  
Aida Bujosa ◽  
Maria Borrell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Cancer Genetics ◽  
Susceptibility Genes ◽  
Breast And Ovarian Cancer ◽  
Eligibility Criteria ◽  
Cancer Susceptibility Genes ◽  
Incident Cancer ◽  
Incident Cases ◽  
Multigene Panel

1582 Background: Despite the use of clinical eligibility criteria and mutation predictive models, a great proportion of families are negative for germline mutations in BRCA1/2 genes. Traditionally, risk assessment of inconclusive results included the recommendation of high-risk surveillance protocol, the update of incident cancer cases in the family and the consideration of additional testing to rule out the possibility of phenocopy. More recently, next generation sequencing multigene panels have become a standard practice in cancer genetics clinics worldwide. We addressed the value of multigene panel retesting of BRCA1/2 negative HBOC families in our institution. Methods: After genetic counseling session and informed consent, a total of 137 individuals (119 probands and 18 extra cancer-affected relatives) from distinct BRCA1/2 negative families were retested using a panel containing 11 breast and ovarian cancer susceptibility genes ( BRCA1/2, PALB2, ATM, CHEK2, PTEN, TP53, STK11, BRIP1, RAD51C, RAD51D). Results: According to the BOADICEA model, the remaining probability of mutation in BRCA1/2 or PALB2 genes in our cohort was 5.5% (0.1-61). The reasons for considering retesting were the addition of any incident cancer diagnosis in 33 cases (24%), a prior study with a low sensitivity screening technique (dHPLC) in 6 families (5%) and the expansion of the study to other putative breast and ovarian susceptibility genes in 98 families (71%). Overall, 3 pathogenic (2 BRCA2, 1 CHEK2) and 8 likely pathogenic variants (1 BRCA2, 4 CHEK2 and 3 ATM) were found. The prevalence was 8%. The detection rate among 19 families with a > 10% remaining probability of mutation in BRCA1/2 and PALB2 genes was 26%. The 3 clinically significant variants in BRCA2 were detected in 2 families and 1 updated cancer family history (BOADICEA remaining probability of 59, 61 and 12%, respectively). Cascade testing was subsequently done in 15 relatives resulting 8 in mutation carriers and 9 true negatives. Conclusions: Our results support the value of updating cancer incident cases and considering expanded panels in selected families.

Ready to clone: CNV detection and breakpoint fine-mapping in breast and ovarian cancer susceptibility genes by high-resolution array CGH

2016 ◽  
Vol 159 (3) ◽  
pp. 585-590 ◽  
Author(s):  
Karl Hackmann ◽  
Franziska Kuhlee ◽  
Elitza Betcheva-Krajcir ◽  
Anne-Karin Kahlert ◽  
Luisa Mackenroth ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Resolution ◽  
Fine Mapping ◽  
Array Cgh ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Breast And Ovarian Cancer ◽  
Cancer Susceptibility Genes ◽  
Cnv Detection

Screening for germline mutations in breast/ovarian cancer susceptibility genes in high-risk families in Israel

2015 ◽  
Vol 155 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Tamar Yablonski-Peretz ◽  
Shani Paluch-Shimon ◽  
Lior Soussan Gutman ◽  
Yulia Kaplan ◽  
Addie Dvir ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Germline Mutations ◽  
Susceptibility Genes ◽  
Cancer Susceptibility Genes ◽  
High Risk Families

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.

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