Evidence map›Paper›PMID 35841038›Full record

ArticleOrphanet journal of rare diseases2022

A clinicopathologic study of malignancy in VCP-associated multisystem proteinopathy.

Alyaa Shmara, Mari Perez-Rosendahl, Kady Murphy, Ashley Kwon, Charles Smith, Virginia Kimonis

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

Article in Orphanet journal of rare diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 48% 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

4 citing papers in PubMed, 3 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

6 authors at 2 institutions in 1 country.

Alyaa ShmaraDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of California-Irvine, Lab and FEDEX: Hewitt Hall, Rm 2038, Health Sciences Rd., Irvine, CA, 92697, USA.
Mari Perez-RosendahlDepartment of Pathology, University of California-Irvine, Irvine, CA, USA.
Kady MurphyDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of California-Irvine, Lab and FEDEX: Hewitt Hall, Rm 2038, Health Sciences Rd., Irvine, CA, 92697, USA.
Ashley KwonDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of California-Irvine, Lab and FEDEX: Hewitt Hall, Rm 2038, Health Sciences Rd., Irvine, CA, 92697, USA.
Charles SmithDepartment of Neurology and Sanders-Brown Center On Aging, University of Kentucky, Lexington, KY, USA.
Virginia KimonisDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of California-Irvine, Lab and FEDEX: Hewitt Hall, Rm 2038, Health Sciences Rd., Irvine, CA, 92697, USA. vkimonis@uci.edu.ORCID 0000-0003-1567-4449
University of California, Irvine · USUniversity of Kentucky · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Genetic basis of myopathy with Paget disease of boneR01AR050236 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KIMONIS, VIRGINIA EUNICE · 2004 to 2008
$1.3M
Translational Studies in VCP Inclusion Body Myopathy with Paget Disease of BoneR56AR050236 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KIMONIS, VIRGINIA EUNICE · 2009 to 2009
$437k
NCATS NIH HHS UL1 TR001414NCI NIH HHS P30 CA062203NIAMS NIH HHS R01 AR050236NIAMS NIH HHS R56 AR050236
6 · The paper itself

Abstract

backgroundValosin containing protein (VCP) is an important protein with many vital functions mostly related to the ubiquitin-proteasome system that provides protein quality control. VCP-associated inclusion body myopathy with Paget disease of bone and frontotemporal dementia, also termed VCP disease and multisystem proteinopathy (MSP 1), is an autosomal dominant disorder caused by monoallelic variants in the VCP gene on human chromosome 9. VCP has also been strongly involved in cancer, with over-activity of VCP found in several cancers such as prostate, pancreatic, endometrial, esophageal cancers and osteosarcoma. Since MSP1 is caused by gain of function variants in the VCP gene, we hypothesized our patients would show increased risk for developing malignancies. We describe cases of 3 rare malignancies and 4 common cancers from a retrospective dataset.

resultsUpon surveying 106 families with confirmed VCP variants, we found a higher rate of rare tumors including malignant peripheral nerve sheath tumor, anaplastic pleomorphic xanthoastrocytoma and thymoma. Some of these subjects developed cancer before displaying other classic VCP disease manifestations. We also present cases of common cancers; however, we did not find an increased rate compared to the general population. This could be related to the early mortality associated with this disease, since most patients die in their 50-60 s due to respiratory failure or cardiomyopathy which is earlier than the age at which most cancers appear.

conclusionThis is the first study that expands the phenotype of VCP disease to potentially include rare cancers and highlights the importance of further investigation of the role of VCP in cancer development. The results of this study in VCP disease patients suggest that patients may be at an increased risk for rare tumors. A larger study will determine if patients with VCP disease develop cancer at a higher rate than the general population. If that is the case, they should be followed up more frequently and screened for recurrence and metastasis of their cancer.

Indexed as

Myositis, Inclusion BodyNeoplasmsValosin Containing ProteinAdenosine TriphosphatasesCell Cycle ProteinsHumansMaleMutationRetrospective StudiesAdenosine TriphosphatasesCell Cycle ProteinsValosin Containing ProteinVCP protein, humanAnaplastic pleomorphic xanthoastrocytomaCancerFrontotemporal dementiaIBMPFDMultisystem proteinopathyMyopathyPaget disease of bonePeripheral nerve sheath tumorThymomaVCP

Identifiers

PMID35841038
PMCPMC9287862
OpenAlexW4285593028

What OpenQuestion holds

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LicenceCC BY
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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.