{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:37:16Z","timestamp":1792798636964,"version":"4.5.0"},"reference-count":34,"publisher":"BMJ","issue":"3","funder":[{"name":"Shanghai Youth Top-notch Talent Support Program and Shanghai Ninth People\u2019s Hospital Excellent Youth Fund Program","award":["JYYQ003"],"award-info":[{"award-number":["JYYQ003"]}],"id":[{"id":"https:\/\/ror.org\/010826a91","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570884"],"award-info":[{"award-number":["81570884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872339"],"award-info":[{"award-number":["81872339"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272642"],"award-info":[{"award-number":["82272642"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["17DZ2260100"],"award-info":[{"award-number":["17DZ2260100"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["17JC1420100"],"award-info":[{"award-number":["17JC1420100"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["19JC1410202"],"award-info":[{"award-number":["19JC1410202"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["19QA1405100"],"award-info":[{"award-number":["19QA1405100"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Ophthalmol"],"accepted":{"date-parts":[[2023,2,24]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Background<\/jats:title>\n                  <jats:p>This study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-centre retrospective cohort study from including 58 AH samples collected from 58 patients diagnosed. Among them, 41 samples were collected after enucleation and 17 samples were collected before intravitreal chemotherapy. SCNAs were accessed by conducting shallow whole-genome sequencing in cell-free (cf) DNA of AH. HRs and ORs were applied to measure risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Canonical RB SCNAs including 1q gain (87%), 2p gain (50%), 6p gain (76%), 16q loss (69%) were frequently detected. Non-classical RB SCNAs in AH including 17q gain (53%), 19q loss (43%), 7q gain (35%) were also commonly observed. 19q loss was significantly more common in patients with cT3c or worse stage than others (p=0.034). 2p gain(p=0.001) and 7q gain(p=0.001) were both more common in patients with primary enucleation than those with previous chemotherapy. Interestingly, both 2p gain (HR=1.933, p=0.027) and 7q gain (HR=2.394, p=0.005) might predict enucleation. Correlation analysis with pathological features among enucleated eyes showed that 19q loss can predict a higher risk for both massive choroid invasion (OR=4.909, p=0.038) and postlaminar optic nerve invasion (OR=4.250, p=0.043).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Sequencing of AH cfDNA in RB can provide sufficient in vivo information. 19q loss was a potential signature of advanced cases clinically and pathologically.<\/jats:p>\n                    <jats:p>Repeated sampling from eyes receiving sequential chemotherapy should be conducted to evaluate fluctuation of SCNA in future study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bjo-2022-322866","type":"journal-article","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T03:49:00Z","timestamp":1679197740000},"page":"449-456","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma"],"prefix":"10.1136","volume":"108","author":[{"given":"Yingxiu","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingpeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8907-9100","authenticated-orcid":false,"given":"Jesse L","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianqun","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7442-1391","authenticated-orcid":false,"given":"Jiayan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6642-7451","authenticated-orcid":false,"given":"Renbing","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"2024022109050588000_108.3.449.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61137-9"},{"key":"2024022109050588000_108.3.449.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2021.09.026"},{"key":"2024022109050588000_108.3.449.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.05.005"},{"key":"2024022109050588000_108.3.449.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(85)34105-2"},{"key":"2024022109050588000_108.3.449.5","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1001\/jamaophthalmol.2017.4097","article-title":"Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma","volume":"135","author":"Berry","year":"2017","journal-title":"JAMA Ophthalmol"},{"key":"2024022109050588000_108.3.449.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.10.029"},{"key":"2024022109050588000_108.3.449.7","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.3390\/cancers13133340","article-title":"Comprehensive somatic copy number analysis using aqueous humor liquid biopsy for retinoblastoma","volume":"13","author":"Kim","year":"2021","journal-title":"Cancers"},{"key":"2024022109050588000_108.3.449.8","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-0369"},{"key":"2024022109050588000_108.3.449.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.10.026"},{"key":"2024022109050588000_108.3.449.10","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13061282","article-title":"Establishing the clinical utility of ctDNA analysis for diagnosis, prognosis, and treatment monitoring of retinoblastoma: the aqueous humor liquid biopsy","volume":"13","author":"Xu","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2024022109050588000_108.3.449.11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1167\/tvst.9.10.30","article-title":"Cell-Free DNA tumor fraction in the aqueous humor is associated with therapeutic response in retinoblastoma patients","volume":"9","author":"Polski","year":"2020","journal-title":"Trans Vis Sci Tech"},{"key":"2024022109050588000_108.3.449.12","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2014-306364"},{"key":"2024022109050588000_108.3.449.13","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2011.289"},{"key":"2024022109050588000_108.3.449.14","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.7.923"},{"key":"2024022109050588000_108.3.449.15","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13040673","article-title":"Recurrent somatic chromosomal abnormalities in relapsed extraocular retinoblastoma","volume":"13","author":"Aschero","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2024022109050588000_108.3.449.16","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.ophtha.2020.05.051","article-title":"A multicenter, international collaborative study for American joint Committee on cancer staging of retinoblastoma: Part II: treatment success and globe salvage","volume":"127","author":"Tomar","year":"2020","journal-title":"Ophthalmology"},{"key":"2024022109050588000_108.3.449.17","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1089\/thy.2016.0224","article-title":"Role of CDKN2C copy number in sporadic medullary thyroid carcinoma","volume":"26","author":"Grubbs","year":"2016","journal-title":"Thyroid"},{"key":"2024022109050588000_108.3.449.18","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-00965-y","article-title":"Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors","volume":"8","author":"Adalsteinsson","year":"2017","journal-title":"Nat Commun"},{"key":"2024022109050588000_108.3.449.19","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-022-03567-5","article-title":"Molecular evolutionary process of advanced gastric cancer during sequential chemotherapy detected by circulating tumor DNA","volume":"20","author":"Xi","year":"2022","journal-title":"J Transl Med"},{"key":"2024022109050588000_108.3.449.20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1158\/1541-7786.495.2.9","article-title":"Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma","volume":"2","author":"Marchong","year":"2004","journal-title":"Mol Cancer Res"},{"key":"2024022109050588000_108.3.449.21","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.8.7921"},{"key":"2024022109050588000_108.3.449.22","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/gcc.22429","article-title":"Genomic landscape of retinoblastoma in rb(-\/-) p130(-\/-) mice resembles human retinoblastoma","volume":"56","author":"Kooi","year":"2017","journal-title":"Genes Chromosomes Cancer"},{"key":"2024022109050588000_108.3.449.23","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70045-7"},{"key":"2024022109050588000_108.3.449.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(02)00681-7"},{"key":"2024022109050588000_108.3.449.25","doi-asserted-by":"publisher","DOI":"10.1002\/1096-911X(20010101)36:1<5::AID-MPO1003>3.0.CO;2-E"},{"key":"2024022109050588000_108.3.449.26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0153323","article-title":"A meta-analysis of retinoblastoma copy numbers refines the list of possible driver genes involved in tumor progression","volume":"11","author":"Kooi","year":"2016","journal-title":"PLoS One"},{"key":"2024022109050588000_108.3.449.27","doi-asserted-by":"crossref","DOI":"10.1038\/srep25264","article-title":"Somatic genomic alterations in retinoblastoma beyond Rb1 are rare and limited to copy number changes","volume":"6","author":"Kooi","year":"2016","journal-title":"Sci Rep"},{"key":"2024022109050588000_108.3.449.28","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.3390\/cancers12092714","article-title":"Clinical, genomic, and pharmacological study of MYCN-amplified Rb1 wild-type metastatic retinoblastoma","volume":"12","author":"Zugbi","year":"2020","journal-title":"Cancers"},{"key":"2024022109050588000_108.3.449.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00300-9"},{"key":"2024022109050588000_108.3.449.30","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12432"},{"key":"2024022109050588000_108.3.449.31","first-page":"1358","article-title":"Loss of heterozygosity at 19q13.3 is associated with locally aggressive neuroblastoma","volume":"7","author":"Mora","year":"2001","journal-title":"Clin Cancer Res"},{"key":"2024022109050588000_108.3.449.32","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1200\/JCO.1987.5.7.1090","article-title":"Elevation of cerebrospinal fluid catecholamine metabolites in patients with intracranial tumors of neuroectodermal origin","volume":"5","author":"Bostrom","year":"1987","journal-title":"J Clin Oncol"},{"key":"2024022109050588000_108.3.449.33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011780117"},{"key":"2024022109050588000_108.3.449.34","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-021-03648-3","article-title":"Clonal fitness inferred from time-series modelling of single-cell cancer genomes","volume":"595","author":"Salehi","year":"2021","journal-title":"Nature"}],"container-title":["British Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bjo-2022-322866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T12:07:33Z","timestamp":1708517253000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjo.bmj.com\/lookup\/doi\/10.1136\/bjo-2022-322866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2,21]]},"published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1136\/bjo-2022-322866"],"URL":"https:\/\/doi.org\/10.1136\/bjo-2022-322866","relation":{},"ISSN":["0007-1161","1468-2079"],"issn-type":[{"value":"0007-1161","type":"print"},{"value":"1468-2079","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}