scholarly journals The Importance of Extended Analysis Using Current Molecular Genetic Methods Based on the Example of a Cohort of 228 Patients with Hereditary Breast and Ovarian Cancer Syndrome

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1483
Author(s):  
Luise D. Resch ◽  
Alrun Hotz ◽  
Andreas D. Zimmer ◽  
Katalin Komlosi ◽  
Nina Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
High Risk ◽  
Molecular Genetic ◽  
Pathogenic Variant ◽  
Molecular Diagnostic ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Extended Analysis ◽  
Pathogenic Gene

In about 20–30% of all women with breast cancer, an increased number of cases of breast cancer can be observed in their family history. However, currently, only 5–10% of all breast cancer cases can be attributed to a pathogenic gene alteration. Molecular genetic diagnostics underwent enormous development within the last 10 years. Next-generation sequencing approaches allow increasingly extensive analyses resulting in the identification of additional candidate genes. In the present work, the germline molecular diagnostic analysis of a cohort of 228 patients with suspected hereditary breast and ovarian cancer syndrome (HBOC) was evaluated. The 27 pathogenic gene variants initially detected are listed, and their distribution in the high-risk BRCA1 and BRCA2 genes is presented in this study. In ten high-risk patients, in whom, to date, no pathogenic variant could be detected, an extended genetic analysis of previously not considered risk genes was performed. Three variants of uncertain significance and one pathogenic variant could be described. This proves the importance of extended analysis using current molecular genetic methods.

Predisposing Genes in Breast and Ovarian Cancer: An Overview

1993 ◽  
Vol 79 (5) ◽  
pp. 291-296 ◽  
Author(s):  
Simon A. Smith ◽  
Bruce A.J. Ponder
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
At Risk ◽  
Chromosome 17 ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Li Fraumeni Syndrome ◽  
Predisposing Genes ◽  
Li Fraumeni ◽  
Cancer Syndromes

The isolation of genes that predispose to familial disease is an important goal in cancer research. The identification of such genes « opens up » the possibility of genetic diagnosis in families so that individuals who are at risk of cancer through inheriting a predisposing mutation can be Identified. Genes that are involved in familial cancer syndromes may also be important in the pathogenesis of sporadic forms of the disease, which are often more common. In the search for genes that predispose to familial breast and ovarian cancer much recent progress has been made. A locus on the long arm of chromosome 17, in the interval 17q12-21, has been identified by genetic linkage, and appears to be responsible for disease in approximately 40 % of breast cancer families and most families that contain breast and ovarian cancer. The region containing this locus, which has been called BRCA1, has been narrowed to a 3-4 cM interval defined by THRA1, the thyroid hormone receptor locus alpha, and D17S183, an anonymous microsatellite polymorphism. Loci other than BRCA1 that have been identified appear not only to predispose to breast and/or ovarian tumors, but to tumors at other sites too. A new locus has been identified on chromosome 2 which is linked to hereditary non-polyposis colorectal cancer (HNPCC). Families with HNPCC are also at risk of endometrial cancer and tumors of the ovary, amongst other cancer sites. Finally, mutations in the p53 gene are inherited in families with Li-Fraumeni syndrome, a rare cancer syndrome predisposing to breast tumors, sarcomas, leukemia and other cancers. Li-Fraumeni syndrome is also the only inherited cancer syndrome that predisposes at least in part to breast cancer where the actual predisposing gene is known. For the other cancer syndromes, the cloning of the predisposing genes is eagerly awaited.

BRCA1 and BRCA2 Mutations in Breast and Ovarian Cancer Syndrome: Reflection on the Creighton University Historical Series of High Risk Families

2006 ◽  
Vol 5 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Olga M. Sinilnikova ◽  
Sylvie Mazoyer ◽  
Colette Bonnardel ◽  
Henry T. Lynch ◽  
Steven A. Narod ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Historical Series ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations ◽  
High Risk Families

scholarly journals Clinical Considerations ofBRCA1- andBRCA2-Mutation Carriers: A Review

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
O. Bougie ◽  
J. I. Weberpals
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Significant Risk ◽  
Surgical Prophylaxis ◽  
Breast And Ovarian Cancer ◽  
Screening Guidelines ◽  
Mutation Carriers ◽  
Clinical Considerations

Individuals who carry an inherited mutation in the breast cancer 1 (BRCA1) andBRCA2genes have a significant risk of developing breast and ovarian cancer over the course of their lifetime. As a result, there are important considerations for the clinician in the counseling, followup and management of mutation carriers. This review outlines salient aspects in the approach to patients at high risk of developing breast and ovarian cancer, including criteria for genetic testing, screening guidelines, surgical prophylaxis, and chemoprevention.

scholarly journals Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 361 ◽  
Author(s):  
Rosalía Quezada Urban ◽  
Clara Díaz Velásquez ◽  
Rina Gitler ◽  
María Rojo Castillo ◽  
Max Sirota Toporek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
High Risk Group ◽  
Cancer Genes ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Variants ◽  
Recurrent Mutations

Hereditary breast and ovarian cancer syndrome (HBOC) represents 5–10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in BRCA1/2 genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including BRCA1/2. In the group of cancer patients 15% (46/300) had a pathogenic variant; 11% (33/300) harbored variants with unknown clinical significance (VUS) and 74% (221/300) were negative. The high-risk group had 22% (6/27) of patients with pathogenic variants, 4% (1/27) had VUS and 74% (20/27) were negative. The most recurrent mutations were the Mexican founder deletion of exons 9-12 and the variant p.G228fs in BRCA1, each found in 5 of 17 patients with alterations in this gene. Rare VUS with potential impact at the protein level were found in 21 genes. Our results show for the first time in the Mexican population a higher contribution of pathogenic alleles in other susceptibility cancer genes (54%) than in BRCA1/2 (46%), highlighting the high locus heterogeneity of HBOC and the necessity of expanding genetic tests for this disease to include broader gene panels.

scholarly journals Non-BRCA1/2 Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer

2019 ◽  
pp. 1-14 ◽  
Author(s):  
Christina Adaniel ◽  
Francisca Salinas ◽  
Juan Manuel Donaire ◽  
Maria Eugenia Bravo ◽  
Octavio Peralta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Genetic Predisposition ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants ◽  
Cancer Program ◽  
Genetic Test Results

PURPOSE Little is known about the genetic predisposition to breast and ovarian cancer among the Chilean population, in particular genetic predisposition beyond BRCA1 and BRCA2 mutations. In the current study, we aim to describe the germline variants detected in individuals who were referred to a hereditary cancer program in Santiago, Chile. METHODS Data were retrospectively collected from the registry of the High-Risk Breast and Ovarian Cancer Program at Clínica Las Condes, Santiago, Chile. Data captured included index case diagnosis, ancestry, family history, and genetic test results. RESULTS Three hundred fifteen individuals underwent genetic testing during the study period. The frequency of germline pathogenic and likely pathogenic variants in a breast or ovarian cancer predisposition gene was 20.3%. Of those patients who underwent testing with a panel of both high- and moderate-penetrance genes, 10.5% were found to have pathogenic or likely pathogenic variants in non- BRCA1/2 genes. CONCLUSION Testing for non- BRCA1 and -2 mutations may be clinically relevant for individuals who are suspected to have a hereditary breast or ovarian cancer syndrome in Chile. Comprehensive genetic testing of individuals who are at high risk is necessary to further characterize the genetic susceptibility to cancer in Chile.

scholarly journals Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769430 ◽  
Author(s):  
Mina Darooei ◽  
Subhadra Poornima ◽  
Bibi Umae Salma ◽  
Gayatri R Iyer ◽  
Akhilesh N Pujar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Cancer Patients ◽  
Pedigree Analysis ◽  
Care Hospital ◽  
Breast Cancer Patients ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Targeted Mutation

Global burden of breast cancer is expected to increase to >2 million new cases every year by 2030 and 10% of these are likely to have hereditary breast and ovarian cancer syndrome. Identifying these individuals by pedigree and BRCA1/2 mutation analyses will enable us to offer targeted mutation testing and appropriate counseling. This study from a tertiary care hospital showed that of the 127 breast cancer patients on treatment during 2014–2015, 24 of them fulfilled the criteria of hereditary breast and ovarian cancer syndrome after detailed verbal autopsy and pedigree analysis, and BRCA1 and 2 next-generation sequencing done after pre-test counseling revealed mutations in 13 cases (54%), these included 9 BRCA1 mutations (69%) and 4 BRCA2 mutation (31%). Subsequent post-test counseling recommended targeted mutation analysis for 64 high-risk members in these 13 families with pathogenic mutations, which will help in surveillance for early detection, appropriate management, and prevention of the disease by decreasing the burden to both family and nation. Results from this preliminary study highlight the importance of genetic counseling, pedigree analysis, and genetic testing. It can be recommended that all oncology units should have a genetic counseling service for providing appropriate support to oncologists, patients, and families to prevent unnecessary testing; however, breast cancer screening program is incomplete without evaluating for hereditary breast and ovarian cancer syndrome.

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