Evidence map›Paper›PMID 35839783›Full record

ArticleNeuropathology and applied neurobiology2022

A gene dosage-dependent effect unveils NBS1 as both a haploinsufficient tumour suppressor and an essential gene for SHH-medulloblastoma.

Marialaura Petroni, Francesca Fabretti, Stefano Di Giulio, Vittoria Nicolis di Robilant, Veronica La Monica, Marta Moretti, Francesca Belardinilli, Francesca Bufalieri, Anna Coppa, Paola Paci and 7 more

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In one paragraph

Article in Neuropathology and applied neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

17 authors at 4 institutions in 3 countries.

Marialaura PetroniDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Francesca FabrettiDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Stefano Di GiulioDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Vittoria Nicolis di RobilantDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Veronica La MonicaDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Marta MorettiDepartment of Experimental Medicine, University La Sapienza, Rome, Italy.
Francesca BelardinilliDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Francesca BufalieriDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Anna CoppaDepartment of Experimental Medicine, University La Sapienza, Rome, Italy.
Paola PaciDepartment of Computer Engineering, Automation and Management, University La Sapienza, Rome, Italy.
Alessandro CorsiDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Enrico De SmaeleDepartment of Experimental Medicine, University La Sapienza, Rome, Italy.
Sonia ConiDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Gianluca CanettieriDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Lucia Di MarcotullioDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Zhao-Qi WangLeibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
Giuseppe GianniniDepartment of Molecular Medicine, University La Sapienza, Rome, Italy.
Sapienza University of Rome · ITIstituto Pasteur · ITIstituto di Analisi dei Sistemi ed Informatica Antonio Ruberti · ITLeibniz Institute on Aging - Fritz Lipmann Institute (FLI) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsInherited or somatic mutations in the MRE11, RAD50 and NBN genes increase the incidence of tumours, including medulloblastoma (MB). On the other hand, MRE11, RAD50 and NBS1 protein components of the MRN complex are often overexpressed and sometimes essential in cancer. In order to solve the apparent conundrum about the oncosuppressive or oncopromoting role of the MRN complex, we explored the functions of NBS1 in an MB-prone animal model. MATERIALS AND

methodsWe generated and analysed the monoallelic or biallelic deletion of the Nbn gene in the context of the SmoA1 transgenic mouse, a Sonic Hedgehog (SHH)-dependent MB-prone animal model. We used normal and tumour tissues from these animal models, primary granule cell progenitors (GCPs) from genetically modified animals and NBS1-depleted primary MB cells, to uncover the effects of NBS1 depletion by RNA-Seq, by biochemical characterisation of the SHH pathway and the DNA damage response (DDR) as well as on the growth and clonogenic properties of GCPs.

resultsWe found that monoallelic Nbn deletion increases SmoA1-dependent MB incidence. In addition to a defective DDR, Nbn

conclusionsOur study indicates that Nbn is haploinsufficient for SHH-MB development whereas full Nbn

Indexed as

Cell Cycle ProteinsCerebellar NeoplasmsDNA-Binding ProteinsMedulloblastomaAnimalsGene DosageGenes, EssentialHedgehog ProteinsMiceMice, TransgenicCell Cycle ProteinsDNA-Binding ProteinsHedgehog ProteinsNijmegen breakage syndrome 1 protein, mouseShh protein, mousehaploinsufficiencyMRN complexNijmegen breakage syndromeNotchSonic Hedgehog

Identifiers

PMID35839783
PMCPMC9542137
OpenAlexW4285589364

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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.