Identification of germline pathogenic variants in DNA damage repair genes by a next-generation sequencing multigene panel in BRCAX patients

Rodríguez-Balada, Marta; Roig, Bárbara; Melé, Mireia; Albacar, Cinta; Serrano, Sara; Salvat, M.; Querol, Montserrat; Borrás, Joan; Martorell, Lourdes; Gumà, Josep

doi:10.1016/j.clinbiochem.2019.11.014

Cited by 10 publications

(10 citation statements)

References 36 publications

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“…Seventy-seven percent of pathogenic and likely pathogenic variants were identified in breast cancer individuals highlighting the importance of multigene testing for identifying variants and VUS in familial breast cancer patients [ 9 ]. A retrospective study among patients with hereditary breast and ovarian cancer with no pathogenic BRCA mutations on initial testing, identified pathogenic/likely pathogenic mutations in genes like PALB2, BRIP1, BARD1, and RAD50 in addition to VUS in TP53, CHEK2, and CDH1 genes [ 10 ]. The inclusion of PALB2 among multigene panels is supported by studies revealing pathogenic/likely pathogenic mutations in the gene [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation and the Role of Multigene Panel Testing for Hereditary Breast Cancer: A Single-Institution Experience

Lu¹,

Smith²,

Kanderi³

et al. 2021

Cureus

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Section: Discussionmentioning

confidence: 99%

Genetic Variation and the Role of Multigene Panel Testing for Hereditary Breast Cancer: A Single-Institution Experience

Lu¹,

Smith²,

Kanderi³

et al. 2021

Cureus

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“…If the patients' personal or family history of cancer indicates that other genes could be relevant, the patient should be referred to genetic counseling [13]. Several studies have reported that offering BC patients testing of multi gene panels results in clinical significant findings in other breast cancer genes [28][29][30][31]. Whether surgeons and oncologists also should offer multi gene panels to BC patients is a continuous discussion in Norway.…”

Section: Discussionmentioning

confidence: 99%

Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway

Grindedal

Jørgensen

Olsson³

et al. 2020

Familial Cancer

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Studies have shown that a significant number of eligible breast cancer patients are not offered genetic testing or referral to genetic counseling. To increase access to genetic testing in South Eastern Norway, testing has since 2014 been offered directly to breast cancer patients by surgeons and oncologists. This practice is termed "mainstreamed genetic testing". The aim of this study was to investigate to what extent patients in South Eastern Norway are offered testing. Three hundred and sixty one patients diagnosed in 2016 and 2017 at one regional and one university hospital in South Eastern Norway were included. Data on whether the patients fulfilled the criteria, whether they had been offered testing and if they were tested were collected. In total, 26.6% (96/361) fulfilled the criteria for testing. Seventy five percent (69/92) of these were offered testing, and 71.7% (66/92) were tested. At the university hospital, 90.2% (37/41) of eligible patients were offered testing, and at the regional hospital 62.7% (32/51). Fifty two percent (12/23) of eligible patient not offered testing were younger than 50 years at time of diagnosis. As many as 95.4% (125/131) of all patients who were offered testing, wanted to be tested. The majority of patients who fulfilled the criteria were offered testing, supporting the practice of mainstreamed genetic testing. There were nevertheless differences in rates of testing between the hospitals that affected all groups of patients, indicating that genetic testing may not be equally accessible to all patients. We suggest that efforts should be made to increase awareness and improve routines for genetic testing of breast cancer patients in Norway.

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“…In silico tools revealed that six of the missense variants are predicted to be potentially pathogenic. A germline copy number deletion and deletion of exon 2 were identified in two BC cases [54,65]. A large (1258 bp) heterozygous germline deletion in intron three was identified by multiplex ligation-dependent probe amplification in BARD1 in a BC case (diagnosed at age 36 years) [68].…”

Section: Multi-gene Panel and Next-generation Sequencing Studies Inclmentioning

confidence: 99%

“…Multi-gene panels that usually contain known high-risk cancer predisposing genes, such as BRCA1 and BRCA2 , were used to determine the prevalence and spectrum of variants in the genes in defined study groups for comparative purposes. Germline whole gene sequencing panels included 10–219 genes [ 16 , 18 , 19 , 20 , 21 , 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 ] and whole exome sequencing strategies analyzed 10–832 genes [ 63 , 64 , 65 , 66 , 67 ]. These sequencing strategies were used in studies on BC and/or OC and male BC, the first being published in 2011 [ 61 ] ( Figure 1 ).…”

Section: Potentially Pathogenic Germline Bard1 mentioning

confidence: 99%

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Alenezi

Fierheller

Recio

et al. 2020

Genes

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Soon after the discovery of BRCA1 and BRCA2 over 20 years ago, it became apparent that not all hereditary breast and/or ovarian cancer syndrome families were explained by germline variants in these cancer predisposing genes, suggesting that other such genes have yet to be discovered. BRCA1-associated ring domain (BARD1), a direct interacting partner of BRCA1, was one of the earliest candidates investigated. Sequencing analyses revealed that potentially pathogenic BARD1 variants likely conferred a low–moderate risk to hereditary breast cancer, but this association is inconsistent. Here, we review studies of BARD1 as a cancer predisposing gene and illustrate the challenge of discovering additional cancer risk genes for hereditary breast and/or ovarian cancer. We selected peer reviewed research articles that focused on three themes: (i) sequence analyses of BARD1 to identify potentially pathogenic germline variants in adult hereditary cancer syndromes; (ii) biological assays of BARD1 variants to assess their effect on protein function; and (iii) association studies of BARD1 variants in family-based and case-control study groups to assess cancer risk. In conclusion, BARD1 is likely to be a low–moderate penetrance breast cancer risk gene.

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Identification of germline pathogenic variants in DNA damage repair genes by a next-generation sequencing multigene panel in BRCAX patients

Cited by 10 publications

References 36 publications

Genetic Variation and the Role of Multigene Panel Testing for Hereditary Breast Cancer: A Single-Institution Experience

Genetic Variation and the Role of Multigene Panel Testing for Hereditary Breast Cancer: A Single-Institution Experience

Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

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