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

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Shreya Sirivolu, Michael J Schmidt, Rishvanth K Prabakar, Peter Kuhn, James Hicks, Jesse L Berry, Liya Xu
{"title":"Single-cell somatic copy number alteration profiling of vitreous humor seeds in retinoblastoma.","authors":"Shreya Sirivolu, Michael J Schmidt, Rishvanth K Prabakar, Peter Kuhn, James Hicks, Jesse L Berry, Liya Xu","doi":"10.1080/13816810.2024.2374886","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Heterogeneity 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.</p><p><strong>Methods: </strong>Aqueous 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.</p><p><strong>Results: </strong>Heatmap 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.</p><p><strong>Conclusions: </strong>Our 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.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmic Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13816810.2024.2374886","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Heterogeneity 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.

Methods: Aqueous 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.

Results: Heatmap 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.

Conclusions: Our 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.

视网膜母细胞瘤玻璃体种子的单细胞体细胞拷贝数改变图谱。
背景:异质性会影响生物标记物的鉴定。因此,我们利用单细胞全基因组图谱研究了视网膜母细胞瘤患者玻璃体液中单个肿瘤细胞的体细胞拷贝数改变(SCNAs),并探讨了玻璃体液和水液、玻璃体种子和肿瘤之间的基因组一致性:从患有视网膜母细胞瘤和玻璃体种子的去核球体中获取房水(AH)、玻璃体(VH)和肿瘤活检组织。通过微操作从玻璃体种子中人工分离出 39 个活体单个肿瘤细胞。通过全基因组测序生成了这些单个细胞的SCNA图谱,并与来自AH和VH的肿瘤块和无细胞DNA(cfDNA)图谱一起进行了分析:VH单细胞SCNA图谱的热图显示了单个玻璃体种子之间的异质性,其中有一个明显占优势的亚克隆(37个细胞中的23个)。该亚克隆细胞的 SCNA 图谱与无细胞 AH 和 VH 的 cfDNA 图谱以及肿瘤图谱的平均一致性为 98%:我们的研究结果揭示了单个 VH 种子中单细胞 SCNA 图谱的一些异质性。尽管存在这种异质性,但优势玻璃体亚克隆与肿瘤和 AH 的 SCNA 图谱具有极高的一致性(>98%),这表明 AH 的 cfDNA 代表了优势基因组亚克隆。这可能有助于通过 AH 鉴定肿瘤生物标记物。这项初步工作支持将单细胞技术应用于视网膜母细胞瘤的 VH 种子,将其作为研究肿瘤亚克隆的平台,从而深入了解疾病基因组的复杂性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Ophthalmic Genetics
Ophthalmic Genetics 医学-眼科学
CiteScore
2.40
自引率
8.30%
发文量
126
审稿时长
>12 weeks
期刊介绍: Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信