Exome Sequencing in BRCA1- and BRCA2-Negative Greek Families Identifies MDM1 and NBEAL1 as Candidate Risk Genes for Hereditary Breast Cancer

Glentis, Stavros; Dimopoulos, Alexandros C.; Rouskas, Konstantinos; Ntritsos, George; Εvangelou, Εvangelos; Narod, Steven A.; Mes‐Masson, Anne‐Marie; Foulkes, William D.; Rivera, Bárbara; Tonin, Patricia N.; Ragoussis, Jiannis; Dimas, Antigone S.

doi:10.3389/fgene.2019.01005

Cited by 16 publications

(17 citation statements)

References 46 publications

(65 reference statements)

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“…A total of 265 studies were further assessed by the full-text review, of which 145 studies not meeting the criteria (described in the Methods section and Figure S1 ) were excluded. Finally, for the analysis, we included 123 studies: 120 studies from the PubMed search and 3 hand-searched studies [ 15 , 16 , 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , …”

Section: Resultsmentioning

confidence: 99%

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

Suszyńska

Kozlowski

2020

Genes

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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.

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Section: Resultsmentioning

confidence: 99%

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

Suszyńska

Kozlowski

2020

Genes

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“…In our research, we found that hsa-miR-1827 regulated the seven upregulated target genes, including GBP6, CEACAM8, C7orf34, KCNV2, OLFM4, NR5A1, and ZNF488. Studies have demonstrated that hsa-miR-1827 and its target(s) are closely associated with breast cancer, cervical cancer, and tongue squamous cell carcinoma [42][43][44][45][46][47][48]; we also explored whether these genes or miRNAs are involved in IDD, and then we further verify the connection of circRNA and IDD by constructing an integrated circRNA-miRNA-mRNA network. For example, the high expression of target genes CEACAM8 and OLFM4 plays a crucial role in the in ammatory process by increasing the level of in ammatory cytokines [49,50].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of a circRNA-miRNA-mRNA Axis in Intervertebral Disc Degeneration

Xiong¹,

Tu²,

Gao³

et al. 2020

Preprint

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Background: Low back pain (LBP) is a common symptom in daily life and one of the primary causes is intervertebral disc degeneration (IDD). Growing studies have indicated that circular RNAs (circRNAs) are intimately associated with IDD; however, the underlying mechanism has not yet been elucidated. We aimed to explore how circRNAs regulate IDD in an effort to provide novel insight for clinical diagnosis and treatment. Methods: The sequencing data of circRNAs, microRNAs (miRNAs), and mRNA were acquired from Gene Expression Omnibus (GEO) datasets. By analyzing the dataset consisting of a control group and degenerated group, differentially expressed circRNAs, miRNAs, and mRNAs were collected, and then the intersection of circRNAs, miRNAs, and mRNAs was screened. According to these intersectional RNAs, we constructed an integrally circRNA-miRNA-mRNA network. Finally, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we further clarified functions of the intersectional mRNA in IDD. Results: we obtained 620 differentially expressed circRNAs(DEcircRNAs), 13 miRNA (DEmiRNA), 273 mRNAs(DEmRNAs), 12 intersectional miRNAs, and 47 intersectional mRNAs. Finally, based on interactional 8 circRNA, 5 miRNAs and 15 mRNAs, an integrally circRNA-miRNA-mRNA network was constructed. Eight circRNAs, contained hsa_circ_0032254, hsa_circ_0003183, hsa_circ_0032253, hsa_circ_0001293, hsa_circ_0004565, hsa_circ_0091570, hsa_circ_0077526, and hsa_circ_0057552, may regulate IDD onset and progression by acting as competing endogenous RNAs. The results of GO and KEGG analyses implied that the targeted genes might significantly correlate to IDD.Conclusion: our findings improved a better understanding of the circRNA-related ceRNA regulatory mechanism in IDD and offered possible targets for IDD treatment.

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“…During the validation phase for this study, 2633 cancer patients and a control group of 2287 adults and 1932 newborns of French-Canadian ancestry were studied (Table 1 ). In detail, 1925 BC including 212 (207 women, 5 men) high-risk cases (age, 19–73; average, 45) in addition to 1201 (all women) moderate risk BC cases (age, 25–68; average, 48) that we previously described in detail 9 and a group of 512 BC diagnosed under 70 years of age 29 , 30 . Briefly, the risk classification of the BC patients depended mainly on the age of diagnosis and presence of family history (high risk = early onset and/or strong family history; moderate risk is defined as age at diagnosis < 50 years or ≥ 50 years but with affected first- or second-degree relatives).…”

Section: Methodsmentioning

confidence: 99%

Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

Elkholi

Iorio

Fahiminiya

et al. 2021

Sci Rep

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The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case–control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations.

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Exome Sequencing in BRCA1- and BRCA2-Negative Greek Families Identifies MDM1 and NBEAL1 as Candidate Risk Genes for Hereditary Breast Cancer

Cited by 16 publications

References 46 publications

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

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

Integrated Analysis of a circRNA-miRNA-mRNA Axis in Intervertebral Disc Degeneration

Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

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