Evidence map›Paper›PMID 34274969›Full record

ArticleHuman molecular genetics2021

Germline ERBB3 mutation in familial non-small-cell lung carcinoma: expanding ErbB's role in oncogenesis.

Aideen M McInerney-Leo, Hui Yi Chew, Po-Ling Inglis, Paul J Leo, Shannon R Joseph, Caroline L Cooper, Satomi Okano, Tim Hassall, Lisa K Anderson, Rayleen V Bowman and 10 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
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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

20 authors at 4 institutions in 2 countries.

Aideen M McInerney-LeoThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.ORCID 0000-0002-0059-5732
Hui Yi ChewThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Po-Ling InglisCancer Care Services, Royal Brisbane and Women's Hospital, Herston QLD 4029, Australia.
Paul J LeoAustralian Translational Genomics Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
Shannon R JosephThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Caroline L CooperDepartment of Anatomical Pathology, Pathology Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
Satomi OkanoThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Tim HassallCentre for Children and Adolescent Brain Cancer, Oncology Department, Queensland Children's Hospital, South Brisbane, QLD 4101, Australia.
Lisa K AndersonCancer Care Services, Royal Brisbane and Women's Hospital, Herston QLD 4029, Australia.
Rayleen V BowmanUniversity of Queensland Thoracic Research Centre, Faculty of Medicine, The University of Queensland, 288 Herston Road, Herston, QLD 4006, Australia.
Michael GattasGenetic Health Queensland, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia.
Jessica E HarrisAustralian Translational Genomics Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
Mhairi S MarshallAustralian Translational Genomics Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
Janet G ShawUniversity of Queensland Thoracic Research Centre, Faculty of Medicine, The University of Queensland, 288 Herston Road, Herston, QLD 4006, Australia.
Lawrie WheelerAustralian Translational Genomics Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
Ian A YangUniversity of Queensland Thoracic Research Centre, Faculty of Medicine, The University of Queensland, 288 Herston Road, Herston, QLD 4006, Australia.
Matthew A BrownAustralian Translational Genomics Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
Kwun M FongUniversity of Queensland Thoracic Research Centre, Faculty of Medicine, The University of Queensland, 288 Herston Road, Herston, QLD 4006, Australia.
Fiona SimpsonThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Emma L DuncanAustralian Translational Genomics Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
The University of Queensland · AUTranslational Research Institute · AURoyal Brisbane and Women's Hospital · AUChildren's Health Queensland Hospital and Health Service · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lung cancer is the commonest cause of cancer deaths worldwide. Although strongly associated with smoking, predisposition to lung cancer is also heritable, with multiple common risk variants identified. Rarely, dominantly inherited non-small-cell lung cancer (NSCLC) has been reported due to somatic mutations in EGFR/ErbB1 and ERBB2. Germline exome sequencing was performed in a multi-generation family with autosomal dominant NSCLC, including an affected child. Tumour samples were also sequenced. Full-length wild-type (wtErbB3) and mutant ERBB3 (mutErbB3) constructs were transfected into HeLa cells. Protein expression, stability, and subcellular localization were assessed, and cellular proliferation, pAkt/Akt and pERK levels determined. A novel germline variant in ERBB3 (c.1946 T > G: p.Iso649Arg), coding for receptor tyrosine-protein kinase erbB-3 (ErbB3), was identified, with appropriate segregation. There was no loss-of-heterozygosity in tumour samples. Both wtErbB3 and mutErbB3 were stably expressed. MutErbB3-transfected cells demonstrated an increased ratio of the 80 kDa form (which enhances proliferation) compared with the full-length (180 kDa) form. MutErbB3 and wtErbB3 had similar punctate cytoplasmic localization pre- and post-epidermal growth factor stimulation; however, epidermal growth factor receptor (EGFR) levels decreased faster post-stimulation in mutErbB3-transfected cells, suggesting more rapid processing of the mutErbB3/EGFR heterodimer. Cellular proliferation was increased in mutErbB3-transfected cells compared with wtErbB3 transfection. MutErbB3-transfected cells also showed decreased pAkt/tAkt ratios and increased pERK/tERK 30 min post-stimulation compared with wtErbB3 transfection, demonstrating altered signalling pathway activation. Cumulatively, these results support this mutation as tumorogenic. This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsCarcinogenesisChildErb-b2 Receptor Tyrosine KinasesGerm CellsGerm-Line MutationHeLa CellsHumansReceptor, ErbB-3Erb-b2 Receptor Tyrosine KinasesERBB3 protein, humanReceptor, ErbB-3

Identifiers

PMID34274969
PMCPMC8643496
OpenAlexW3185870948

What OpenQuestion 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 OpenQuestion graph.