Increased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition

2022 ◽  
Author(s):  
P. Macquere ◽  
S. Orazio ◽  
F. Bonnet ◽  
N. Jones ◽  
V. Bubien ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Predisposition ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Variants

scholarly journals Non-Coding Variants in BRCA1 and BRCA2 Genes: Potential Impact on Breast and Ovarian Cancer Predisposition

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 453 ◽  
Author(s):  
Elizabeth Santana dos Santos ◽  
François Lallemand ◽  
Leslie Burke ◽  
Dominique Stoppa-Lyonnet ◽  
Melissa Brown ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Predisposition ◽  
Gene Promoters ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Coding Regions ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Donor And Acceptor ◽  
The Impact

BRCA1 and BRCA2 are major breast cancer susceptibility genes whose pathogenic variants are associated with a significant increase in the risk of breast and ovarian cancers. Current genetic screening is generally limited to BRCA1/2 exons and intron/exon boundaries. Most identified pathogenic variants cause the partial or complete loss of function of the protein. However, it is becoming increasingly clear that variants in these regions only account for a small proportion of cancer risk. The role of variants in non-coding regions beyond splice donor and acceptor sites, including those that have no qualitative effect on the protein, has not been thoroughly investigated. The key transcriptional regulatory elements of BRCA1 and BRCA2 are housed in gene promoters, untranslated regions, introns, and long-range elements. Within these sequences, germline and somatic variants have been described, but the clinical significance of the majority is currently unknown and it remains a significant clinical challenge. This review summarizes the available data on the impact of variants on non-coding regions of BRCA1/2 genes and their role on breast and ovarian cancer predisposition.

scholarly journals Summary of BARD1 Mutations and Precise Estimation of Breast and Ovarian Cancer Risks Associated with the Mutations

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 798
Author(s):  
Malwina Suszynska ◽  
Piotr Kozlowski
Keyword(s):  
Ovarian Cancer ◽  
Diagnostic Testing ◽  
Cancer Risks ◽  
Breast And Ovarian Cancer ◽  
Moderate Risk ◽  
Risk Gene ◽  
Pathogenic Variants ◽  
Precise Estimation ◽  
Evidence Based Guidelines

Over the last two decades, numerous BARD1 mutations/pathogenic variants (PVs) have been found in patients with breast cancer (BC) and ovarian cancer (OC). However, their role in BC and OC susceptibility remains controversial, and strong evidence-based guidelines for carriers are not yet available. Herein, we present a comprehensive catalog of BARD1 PVs identified in large cumulative cohorts of ~48,700 BC and ~20,800 OC cases (retrieved from 123 studies examining the whole coding sequence of BARD1). Using these resources, we compared the frequency of BARD1 PVs in the cases and ~134,100 controls from the gnomAD database and estimated the effect of the BARD1 PVs on BC and OC risks. The analysis revealed that BARD1 is a BC moderate-risk gene (odds ratio (OR) = 2.90, 95% CIs:2.25–3.75, p < 0.0001) but not an OC risk gene (OR = 1.36, 95% CIs:0.87–2.11, p = 0.1733). In addition, the BARD1 mutational spectrum outlined in this study allowed us to determine recurrent PVs and evaluate the variant-specific risk for the most frequent PVs. In conclusion, these precise estimates improve the understanding of the role of BARD1 PVs in BC and OC predisposition and support the need for BARD1 diagnostic testing in BC patients.

scholarly journals Corrigendum to ``Survey of gynecological carcinosarcomas in families with breast and ovarian cancer predisposition'' [Cancer Genet. 221(2018) 38–45]

2018 ◽  
Vol 228-229 ◽  
pp. 128
Author(s):  
C.B. Ripamonti ◽  
S. Manoukian ◽  
B. Peissel ◽  
J. Azzollini ◽  
M.L. Carcangiu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Predisposition ◽  
Breast And Ovarian Cancer

Survey of gynecological carcinosarcomas in families with breast and ovarian cancer predisposition

2018 ◽  
Vol 221 ◽  
pp. 38-45 ◽  
Author(s):  
Carla B. Ripamonti ◽  
Siranoush Manoukian ◽  
Bernard Peissel ◽  
Jacopo Azzollini ◽  
Maria Luisa Carcangiu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Predisposition ◽  
Breast And Ovarian Cancer

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.

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