Evidence map›Paper›PMID 39016001›Full record

ArticleOphthalmic genetics2024

Single-cell somatic copy number alteration profiling of vitreous humor seeds in retinoblastoma.

Shreya Sirivolu, Michael J Schmidt, Rishvanth K Prabakar, Peter Kuhn, James Hicks, Jesse L Berry, Liya Xu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Ophthalmic genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma.Investigative ophthalmology & visual science · 2025
    Article
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

7 authors.

Shreya SirivoluThe Vision Center, Children's Hospital Los Angeles, Los Angeles, California, USA.
Michael J SchmidtConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, USA.
Rishvanth K PrabakarConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, USA.
Peter KuhnConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, USA.
James HicksConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, USA.
Jesse L BerryThe Vision Center, Children's Hospital Los Angeles, Los Angeles, California, USA.
Liya XuThe Vision Center, Children's Hospital Los Angeles, Los Angeles, California, USA.

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI William Dean Wallace · 1985 to 2026
$181.4M
Ophthalmic Therapeutics Engineering CoreP30EY029220 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Mahnaz Shahidi · 2018 to 2026
$6.5M
Validation of an aqueous humor liquid biopsy for molecular prognostication and monitoring of children with retinoblastoma.R01CA282759 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI Jesse L Berry · 2023 to 2026
$2.2M
Development of a surrogate liquid biopsy from the aqueous humor in retinoblastoma eyes.K08CA232344 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI BERRY, JESSE L · 2018 to 2022
$1.1M
NCI NIH HHS K08 CA232344NCI NIH HHS P30 CA014089NCI NIH HHS R01 CA282759NEI NIH HHS P30 EY029220
6 · The paper itself

Abstract

backgroundHeterogeneity can impact biomarker identification. Thus, we investigated the somatic copy number alterations (SCNAs) of individual tumor cells in the vitreous humor of a retinoblastoma patient using single-cell whole-genome profiling and explored the genomic concordance among vitreous and aqueous humor, vitreous seeds, and tumor.

methodsAqueous humor (AH), vitreous humor (VH), and tumor biopsy were obtained from an enucleated globe with retinoblastoma and vitreous seeding. Micromanipulation was used to manually isolate 39 live single tumor cells from vitreous seeds harvested from the VH. The SCNA profiles of these individual cells were generated via whole-genome sequencing and analyzed alongside profiles from the tumor mass and cell-free DNA (cfDNA) from AH and VH.

resultsHeatmap of VH single-cell SCNA profiles demonstrates heterogeneity among individual vitreous seeds with one clearly dominant subclone (23 of 37 cells). The SCNA profiles from the cells in this subclone demonstrate an average concordance of 98% with cfDNA profiles from acellular AH and VH and with the tumor profile.

conclusionsOur findings reveal some heterogeneity among single-cell SCNA profiles in individual VH seeds. Despite this heterogeneity, the dominant vitreous subclone exhibits extremely (>98%) high concordance with the SCNA profile from tumor and AH, suggesting AH cfDNA is representative of the dominant genomic subclone. This may facilitate tumoral biomarker identification via the AH. This preliminary work supports the potential of applying single-cell technology to VH seeds in retinoblastoma as a platform to study tumor subclones, which may provide insight into the genomic complexity of disease.

Indexed as

Aqueous HumorDNA Copy Number VariationsRetinal NeoplasmsRetinoblastomaSingle-Cell AnalysisVitreous BodyBiomarkers, TumorCell-Free Nucleic AcidsFemaleHumansMaleBiomarkers, TumorCell-Free Nucleic Acidsaqueous humorcell-free DNAcirculating tumor DNAliquid biopsyprecision oncologyRetinoblastomasomatic copy number alterationvitreous humor

Identifiers

PMID39016001
PMCPMC11598666

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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.