Evidence mapPaperPMID 34072463Full record

ReviewInternational journal of molecular sciences2021

Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?

Roberta Zuntini, Elena Bonora, Laura Maria Pradella, Laura Benedetta Amato, Michele Vidone, Sara De Fanti, Irene Catucci, Laura Cortesi, Veronica Medici, Simona Ferrari and 4 more

Open access · goldAbstract readCase ReportsReview
In one paragraph

Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
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 4 institutions in 1 country.

Roberta ZuntiniCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Elena BonoraCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Laura Maria PradellaCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Laura Benedetta AmatoCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Michele VidoneCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Sara De FantiDepartment of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy.
Irene CatucciIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy.
Laura CortesiDepartment of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41125 Modena, Italy.
Veronica MediciDepartment of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41125 Modena, Italy.
Simona FerrariCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Giuseppe GasparreCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Paolo PeterlongoIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy.ORCID 0000-0001-6951-6855
Marco SazziniDepartment of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy.
Daniela TurchettiCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
Azienda USL di Bologna · ITAzienda Ospedaliero-Universitaria di Modena · ITIFOM · ITUniversity of Bologna · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels.

Indexed as

Genetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationAdultAllelesBreast NeoplasmsCase-Control StudiesCell Cycle ProteinsDNA Mutational AnalysisFemaleGene Expression Regulation, NeoplasticGenetic TestingGenotypeHaplotypesHumansNuclear ProteinsCell Cycle ProteinsNBN protein, humanNuclear Proteinshereditary breast cancerNBNnibrinvariants

Identifiers

PMID34072463
PMCPMC8198239
OpenAlexW3164408238

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.