Evidence map›Paper›PMID 37085799›Full record

ArticleBMC cancer2023

Functional analyses of rare germline BRCA1 variants by transcriptional activation and homologous recombination repair assays.

Nicola Bassi, Henrikke Nilsen Hovland, Kashif Rasheed, Elisabeth Jarhelle, Nikara Pedersen, Eunice Kabanyana Mchaina, Sara Marie Engelsvold Bakkan, Nina Iversen, Hildegunn Høberg-Vetti, Bjørn Ivar Haukanes and 4 more

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Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Nicola Bassi *Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, Tromsø, Norway.
Henrikke Nilsen Hovland *Familial Cancer Center, Haukeland University Hospital, Bergen, Norway.
Kashif RasheedDepartment of Medical Biology, University of Tromsø, Tromsø, Norway.
Elisabeth JarhelleDepartment of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, Tromsø, Norway.
Nikara PedersenDepartment of Biological Sciences, University of Bergen, Bergen, Norway.
Eunice Kabanyana MchainaFamilial Cancer Center, Haukeland University Hospital, Bergen, Norway.
Sara Marie Engelsvold BakkanDepartment of Biological Sciences, University of Bergen, Bergen, Norway.
Nina IversenDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Hildegunn Høberg-VettiFamilial Cancer Center, Haukeland University Hospital, Bergen, Norway.
Bjørn Ivar HaukanesDepartment of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Per Morten KnappskogDepartment of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Ingvild AukrustDepartment of Medical Genetics, Haukeland University Hospital, Bergen, Norway. Ingvild.aukrust@helse-bergen.no.
Elisabet Ognedal *Familial Cancer Center, Haukeland University Hospital, Bergen, Norway.
Marijke Van Ghelue *Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, Tromsø, Norway.
Haukeland University Hospital · NOUiT The Arctic University of Norway · NOUniversity Hospital of North Norway · NOUniversity of Bergen · NOOslo University Hospital · NO

Funding

Helse Vest F-10199/4800001941Kreftforeningen 194643-2017
6 · The paper itself

Abstract

backgroundDamaging alterations in the BRCA1 gene have been extensively described as one of the main causes of hereditary breast and ovarian cancer (HBOC). BRCA1 alterations can lead to impaired homologous recombination repair (HRR) of double-stranded DNA breaks, a process which involves the RING, BRCT and coiled-coil domains of the BRCA1 protein. In addition, the BRCA1 protein is involved in transcriptional activation (TA) of several genes through its C-terminal BRCT domain.

methodsIn this study, we have investigated the effect on HRR and TA of 11 rare BRCA1 missense variants classified as variants of uncertain clinical significance (VUS), located within or in close proximity to the BRCT domain, with the aim of generating additional knowledge to guide the correct classification of these variants. The variants were selected from our previous study "BRCA1 Norway", which is a collection of all BRCA1 variants detected at the four medical genetic departments in Norway.

resultsAll variants, except one, showed a significantly reduced HRR activity compared to the wild type (WT) protein. Two of the variants (p.Ala1708Val and p.Trp1718Ser) also exhibited low TA activity similar to the pathogenic controls. The variant p.Trp1718Ser could be reclassified to likely pathogenic. However, for ten of the variants, the total strength of pathogenic evidence was not sufficient for reclassification according to the CanVIG-UK BRCA1/BRCA2 gene-specific guidelines for variant interpretation.

conclusionsWhen including the newly achieved functional evidence with other available information, one VUS was reclassified to likely pathogenic. Eight of the investigated variants affected only one of the assessed activities of BRCA1, highlighting the importance of comparing results obtained from several functional assays to better understand the consequences of BRCA1 variants on protein function. This is especially important for multifunctional proteins such as BRCA1.

Indexed as

Breast NeoplasmsGenes, BRCA1Recombinational DNA RepairTranscriptional ActivationBRCA1 ProteinFemaleGenetic Predisposition to DiseaseGerm CellsHumansBRCA1 ProteinBRCA1 protein, humanBRCA1Functional assayHereditary breast and ovarian cancerHomologous recombination repairTranscriptional activation

Identifiers

PMID37085799
PMCPMC10122298
OpenAlexW4366606377

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.