Evidence map›Paper›PMID 32139107›Full record

ArticleOphthalmology2020

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.

Armin R Afshar, Melike Pekmezci, Michele M Bloomer, Nicola J Cadenas, Meredith Stevers, Anuradha Banerjee, Ritu Roy, Adam B Olshen, Jessica Van Ziffle, Courtney Onodera and 5 more

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

Article in Ophthalmology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

37 citing papers in PubMed, 74 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

15 authors at 1 institution in 2 countries.

Armin R AfsharDepartment of Ophthalmology, University of California, San Francisco, San Francisco, California; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California. Electronic address: Armin.Afshar@ucsf.edu.
Melike PekmezciDepartment of Ophthalmology, University of California, San Francisco, San Francisco, California; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Department of Pathology, University of California, San Francisco, San Francisco, California.
Michele M BloomerDepartment of Ophthalmology, University of California, San Francisco, San Francisco, California; Department of Pathology, University of California, San Francisco, San Francisco, California.
Nicola J CadenasCancer Genetics and Prevention Program, University of California, San Francisco, San Francisco, California.
Meredith SteversDepartment of Pathology, University of California, San Francisco, San Francisco, California.
Anuradha BanerjeeHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Division of Hematology-Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, California.
Ritu RoyHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Computational Biology and Informatics, University of California, San Francisco, San Francisco, California.
Adam B OlshenHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Computational Biology and Informatics, University of California, San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
Jessica Van ZiffleDepartment of Pathology, University of California, San Francisco, San Francisco, California; Clinical Cancer Genomics Laboratory, University of California, San Francisco, San Francisco, California.
Courtney OnoderaDepartment of Pathology, University of California, San Francisco, San Francisco, California; Clinical Cancer Genomics Laboratory, University of California, San Francisco, San Francisco, California.
W Patrick DevineDepartment of Pathology, University of California, San Francisco, San Francisco, California; Clinical Cancer Genomics Laboratory, University of California, San Francisco, San Francisco, California.
James P GrenertDepartment of Pathology, University of California, San Francisco, San Francisco, California; Clinical Cancer Genomics Laboratory, University of California, San Francisco, San Francisco, California.
Boris C BastianHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Department of Pathology, University of California, San Francisco, San Francisco, California; Clinical Cancer Genomics Laboratory, University of California, San Francisco, San Francisco, California; Department of Dermatology, University of California, San Francisco, San Francisco, California.
David A SolomonHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Department of Pathology, University of California, San Francisco, San Francisco, California; Clinical Cancer Genomics Laboratory, University of California, San Francisco, San Francisco, California.
Bertil E DamatoDepartment of Ophthalmology, University of California, San Francisco, San Francisco, California; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
University of California, San Francisco · US

Funding

Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAMBA, DEEPAK ASHOK · 1985 to 2024
$16.8M
Cohesin gene mutations in tumorigenesisDP5OD021403 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SOLOMON, DAVID A. · 2015 to 2019
$2.0M
Predicting ocular outcomes, quality of life and survival after proton beam radiotherapy of choroidal melanomaK23EY027466 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AFSHAR, ARMIN REZA · 2017 to 2021
$1.1M
NEI NIH HHS K23 EY027466NEI NIH HHS P30 EY002162NIH HHS DP5 OD021403
6 · The paper itself

Abstract

purposeTo determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma.

designCohort study.

participantsThirty-two children with retinoblastoma.

methodsWe performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing.

main outcome measuresPresence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features.

resultsGermline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease.

conclusionsComprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.

Indexed as

Gene SilencingGerm-Line MutationChildChild, PreschoolCohort StudiesDNA Mutational AnalysisDNA, NeoplasmEye EnucleationFemaleHigh-Throughput Nucleotide SequencingHumansInfantMaleParaffin EmbeddingRetinal NeoplasmsRetinoblastomaDNA, NeoplasmRB1 protein, humanRetinoblastoma Binding ProteinsUbiquitin-Protein Ligases

Identifiers

PMID32139107
PMCPMC7246167
OpenAlexW2996000777

What OpenQuestion holds

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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.