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.

Retesting of women who are negative for a BRCA1 and BRCA2 mutation using a 20-gene panel

2019 ◽  
Vol 57 (6) ◽  
pp. 380-384 ◽  
Author(s):  
Jordan Lerner-Ellis ◽  
Victoria Sopik ◽  
Andrew Wong ◽  
Conxi Lázaro ◽  
Steven A Narod ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Brca2 Mutation ◽  
Pathogenic Variant ◽  
Cancer Genes ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Variant Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes

BackgroundThe value of retesting women who previously tested negative for a pathogenic variant (mutation) in BRCA1 and BRCA2 using an expanded panel of breast and ovarian cancer genes is unclear.MethodsWe studied 110 BRCA1/2-negative women who were retested using a panel of 20 breast and/or ovarian cancer susceptibility genes at the Advanced Molecular Diagnostics Laboratory (AMDL) at Mount Sinai Hospital in Toronto between March 2017 and March 2019. All patients had previously tested negative for BRCA pathogenic variants at the AMDL between January 2012 and March 2018 and were subsequently referred for retesting by their physician.ResultsOverall, six pathogenic variants in genes other than BRCA1 and BRCA2 were found (prevalence 5.5%). There were two pathogenic variants found in RAD51C, and one found in each of BRIP1, PALB2, PMS2 and PTEN. The prevalence of pathogenic variants was 6.5% for women affected with cancer (6 of 93), including 4.9% for women with breast cancer (4 of 82) and 22.2% for women with ovarian cancer (2 of 9). None of the 17 unaffected women had a clinically significant or pathogenic variant. There were 44 women (40%) for whom the result of the panel test was inconclusive due to the detection of a variant of uncertain significance.ConclusionsOur findings indicate that the retesting of BRCA1/2-negative individuals with an expanded panel of 20 breast and ovarian cancer genes can produce clinically relevant results, with a yield of 5.5% for pathogenic variants in genes other than BRCA1 and BRCA2.

scholarly journals The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants

2019 ◽  
Vol 144 (11) ◽  
pp. 2683-2694 ◽  
Author(s):  
Stephanie Schubert ◽  
Jana L. Luttikhuizen ◽  
Bernd Auber ◽  
Gunnar Schmidt ◽  
Winfried Hofmann ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
High Frequency ◽  
Pathogenic Variants

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 Hereditary pancreatic cancer

2021 ◽  
Author(s):  
Kodai Abe ◽  
Minoru Kitago ◽  
Yuko Kitagawa ◽  
Akira Hirasawa
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Precision Medicine ◽  
Cancer Patients ◽  
Genome Wide Association Study ◽  
Parp Inhibitor ◽  
Cancer Syndrome ◽  
Germline Variants ◽  
Panel Testing ◽  
Pathogenic Variants

AbstractPancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

scholarly journals Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Huan Wang ◽  
Qi Cheng ◽  
Kaikai Chang ◽  
Lingjie Bao ◽  
Xiaofang Yi
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
M2 Macrophage ◽  
Gynecological Malignancy

Ovarian cancer remains the most lethal gynecological malignancy. Ferroptosis, a specialized form of iron-dependent, nonapoptotic cell death, plays a crucial role in various cancers. However, the contribution of ferroptosis to ovarian cancer is poorly understood. Here, we characterized the diagnostic, prognostic, and therapeutic value of ferroptosis-related genes in ovarian cancer by analyzing transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A reliable 10-gene ferroptosis signature (HIC1, ACSF2, MUC1, etc.) for the diagnosis of ovarian cancer was identified. Notably, we constructed and validated a novel prognostic signature including three FRGs: HIC1, LPCAT3, and DUOX1. We also further developed a risk score model based on these three genes which divided ovarian cancer patients into two risk groups. Functional analysis revealed that immune response and immune-related pathways were enriched in the high-risk group. Meanwhile, the tumor microenvironment was distinct between the two groups, with more M2 Macrophage infiltration and higher expression of key immune checkpoint molecules in the high-risk group than in the other group. Low-risk patients exhibited more favorable immunotherapy and chemotherapy responses. We conclude that crosstalk between ferroptosis and immunity may contribute to the worse prognosis of patients in the high-risk group. In particular, HIC1 showed both diagnostic and prognostic value in ovarian cancer. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients.

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