A Systematic Genetic Assessment of 1,433 Sequence Variants of Unknown Clinical Significance in the BRCA1 and BRCA2 Breast Cancer–Predisposition Genes

2008 ◽  
Vol 2008 ◽  
pp. 302-303
Author(s):  
L.P. Shulman
Keyword(s):  
Breast Cancer ◽  
Clinical Significance ◽  
Cancer Predisposition ◽  
Sequence Variants ◽  
Brca1 And Brca2 ◽  
Breast Cancer Predisposition ◽  
Predisposition Genes ◽  
Genetic Assessment

scholarly journals Correction: DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes

2018 ◽  
Vol 21 (7) ◽  
pp. 1669-1669
Author(s):  
Marcy E. Richardson ◽  
Hansook Chong ◽  
Wenbo Mu ◽  
Blair R. Conner ◽  
Vickie Hsuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Predisposition ◽  
Breast Cancer Predisposition ◽  
Predisposition Genes

scholarly journals DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes

2018 ◽  
Vol 21 (3) ◽  
pp. 683-693 ◽  
Author(s):  
Marcy E. Richardson ◽  
Hansook Chong ◽  
Wenbo Mu ◽  
Blair R. Conner ◽  
Vickie Hsuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Predisposition ◽  
Breast Cancer Predisposition ◽  
Predisposition Genes

scholarly journals Plasma Metabolome Signature Indicative of BRCA1 Germline Status Independent of Cancer Incidence

2021 ◽  
Vol 11 ◽  
Author(s):  
Judith Penkert ◽  
Andre Märtens ◽  
Martin Seifert ◽  
Bernd Auber ◽  
Katja Derlin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Cancer Predisposition ◽  
Metabolic Reprogramming ◽  
Metabolic Effects ◽  
Tissue Integrity ◽  
Breast Cancer Predisposition ◽  
Plasma Metabolome ◽  
Predisposition Genes ◽  
Unknown Structure

Individuals carrying a pathogenic germline variant in the breast cancer predisposition gene BRCA1 (gBRCA1+) are prone to developing breast cancer. Apart from its well-known role in DNA repair, BRCA1 has been shown to powerfully impact cellular metabolism. While, in general, metabolic reprogramming was named a hallmark of cancer, disrupted metabolism has also been suggested to drive cancer cell evolution and malignant transformation by critically altering microenvironmental tissue integrity. Systemic metabolic effects induced by germline variants in cancer predisposition genes have been demonstrated before. Whether or not systemic metabolic alterations exist in gBRCA1+ individuals independent of cancer incidence has not been investigated yet. We therefore profiled the plasma metabolome of 72 gBRCA1+ women and 72 age-matched female controls, none of whom (carriers and non-carriers) had a prior cancer diagnosis and all of whom were cancer-free during the follow-up period. We detected one single metabolite, pyruvate, and two metabolite ratios involving pyruvate, lactate, and a metabolite of yet unknown structure, significantly altered between the two cohorts. A machine learning signature of metabolite ratios was able to correctly distinguish between gBRCA1+ and controls in ~82%. The results of this study point to innate systemic metabolic differences in gBRCA1+ women independent of cancer incidence and raise the question as to whether or not constitutional alterations in energy metabolism may be involved in the etiology of BRCA1-associated breast cancer.

scholarly journals Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast

2021 ◽  
Author(s):  
Siddhartha Yadav ◽  
Chunling Hu ◽  
Katherine L. Nathanson ◽  
Jeffrey N. Weitzel ◽  
David E. Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lobular Carcinoma ◽  
Population Based ◽  
Cancer Predisposition ◽  
Clinical Cohort ◽  
Breast Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Multigene Panel

PURPOSE To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC). RESULTS The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC. CONCLUSION The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.

scholarly journals Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon

2019 ◽  
Vol 29 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Babatunde Adedokun ◽  
Yonglan Zheng ◽  
Paul Ndom ◽  
Antony Gakwaya ◽  
Timothy Makumbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Predisposition ◽  
Breast Cancer Predisposition ◽  
Predisposition Genes ◽  
Inherited Mutations

Germline pathogenic variants in cancer predisposition genes among women with invasive lobular cancer of breast.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10581-10581
Author(s):  
Siddhartha Yadav ◽  
Chunling Hu ◽  
Susan M. Domchek ◽  
Jeffrey N. Weitzel ◽  
David Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Population Based ◽  
Cancer Predisposition ◽  
Clinical Cohort ◽  
Breast Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Multigene Panel Testing ◽  
Multigene Panel

10581 Background: The prevalence of germline pathogenic variants (PVs) in cancer predisposition genes among women with invasive lobular breast cancer (ILC) and the risk of ILC in PV carriers is not well-defined. Methods: The study included 2,999 women with ILC and 32,544 unaffected controls from a population-based cohort; 3,796 women with ILC and 20,323 women with invasive ductal carcinoma (IDC) undergoing clinical multigene panel testing (clinical cohort); and 125,748 exome sequences from unrelated women without a cancer diagnosis in the gnomAD 3.0 dataset. Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected controls in both cohorts and between women with ILC and IDC in the clinical cohort. Results: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analyses, CDH1 and BRCA2 PVs were associated with high risks of ILC (Odds ratio (OR) > 4), and CHEK2, ATM and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. PV frequencies in these genes in ILC and IDC were similar except for PV frequencies in BRCA1 and CDH1. Conclusions: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2 and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. While, multigene panel testing may be appropriate for women with ILC, CDH1 should be specifically discussed in the context of low prevalence and attendant gastric cancer risk.

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