Evidence map›Paper›PMID 32385852›Full record

ArticleJournal of endocrinological investigation2021

BROX haploinsufficiency in familial nonmedullary thyroid cancer.

D Pasquali, A Torella, G Accardo, D Esposito, F Del Vecchio Blanco, D Salvatore, P Sabatino, F Pacini, F Barbato, M G Castagna and 2 more

Abstract read
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In one paragraph

Article in Journal of endocrinological investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Genetic susceptibility to hereditary non-medullary thyroid cancer.Hereditary cancer in clinical practice · 2022
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
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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

12 authors at 6 institutions in 2 countries.

D PasqualiDepartment of Medical and Surgical Advanced Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. daniela.pasquali@unicampania.it.
A TorellaGenetica Medica, Dipartimento di Medicina di Precisione, University of Campania"Luigi Vanvitelli", Naples, Italy.
G AccardoDepartment of Medical and Surgical Advanced Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
D EspositoDepartment of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
F Del Vecchio BlancoGenetica Medica, Dipartimento di Medicina di Precisione, University of Campania"Luigi Vanvitelli", Naples, Italy.
D SalvatoreDepartment of Public Health, University of Naples "Federico II", Naples, Italy.
P SabatinoAzienda Sanitaria Locale Salerno, Naples, Italy.
F PaciniDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
F BarbatoDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
M G CastagnaDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
S CantaraDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
V NigroGenetica Medica, Dipartimento di Medicina di Precisione, University of Campania"Luigi Vanvitelli", Naples, Italy.
University of Siena · ITUniversity of Campania "Luigi Vanvitelli" · ITTelethon Institute Of Genetics And Medicine · ITASL Roma · ITSahlgrenska University Hospital · SEUniversity of Naples Federico II · IT

Funding

Fondazione Telethon H2020-HEALTH - SC1-2017-RTD: "SOLVE RDFondazione Telethon PON01_02418
6 · The paper itself

Abstract

backgroundThe familial nonmedullary thyroid cancer (FNMTC) is suspected to be a Mendelian condition in up to 3-8% of thyroid cancers. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. The inheritance of FNMTC appears to be autosomal dominant with incomplete penetrance and variable expressivity. The finding of the causative gene of FNMTC and the identification of patients at risk that need genetic testing were our aim.

methodsWe analyzed by whole-exome sequencing patients and non-affected relatives of five families with at least two family members affected by papillary thyroid cancer, selecting for new or extremely rare variants with predicted pathogenic value.

resultsA family showed, in all three affected members, a new loss-of-function variant (frameshift deletion) in BROX gene at 1q41 that was absent from all internal and external databases. In a second family with three affected relatives, we found an additional new BROX variant. The smaller families presented no variants in BROX or in the other causative genes studied.

conclusionsBROX could be a new causative gene for FNMTC. Variants in BROX may result in the haploinsufficiency of a key gene involved in the morphogenesis of MVBs, in the endosomal sorting of cargo proteins, and in EGFR. Functional studies are needed to support this result. The thorough genomic analysis by NGS in all families with three or more affected members should become a routine approach to obtain a comprehensive genetic view and find confirmative second cases.

Indexed as

Genetic Predisposition to DiseaseGerm-Line MutationHaploinsufficiencyAdultEndosomal Sorting Complexes Required for TransportFemaleGenetic TestingHumansMaleMiddle AgedPrognosisThyroid Cancer, PapillaryThyroid NeoplasmsBROX protein, humanEndosomal Sorting Complexes Required for TransportBROXEGFRFNMTCHABP2NGSThyroidThyroid cancer

Identifiers

PMID32385852
OpenAlexW3023863706

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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.