Ocular Oncology - Feasibility of Low-Pass Whole Genome Sequencing for Detecting Somatic Copy Number Alterations in Formalin-Fixed Uveal Melanoma Specimens

Sep 28, 2026

Low-pass whole genome sequencing (LP-WGS), leveraging genome-wide coverage from ×0.5 to ×5.0, was assessed for feasibility and clinical utility in detecting somatic copy number alterations (SCNAs) using formalin-fixed paraffin-embedded uveal melanoma tissues. A retrospective cohort of 11 Taiwanese patients was analyzed after enucleation (2007–2021), including samples with prior radiotherapy. LP-WGS identified SCNAs in most tumors and showed associations involving monosomy 3, prognosis-related chromosomal changes, and BAP1 expression.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Purpose

Methods

Results

Conclusions

Ocular Oncology Feasibility of Low-Pass Whole Genome Sequencing for Detecting Somatic Copy Number Alterations in Formalin-Fixed Uveal Melanoma Specimens Chen-Yang Huang 1,*, Ren-Chin Wu2,*, Angel Chao3,4,*, Chien-Hsing Lin5, Chiao-Yun Lin3,4, Yun-Shien Lee6, Yueh-Ju Tsai7, Kuan-Jen Chen7, and An-Ning Chao7 1 Department of Medical Oncology and Genome Medicine Core Laboratory, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan 2 Department of Anatomical Pathology, Chang Gung Memorial Hospital at Linkou, and Chang Gung University College of Medicine, Taoyuan, Taiwan 3 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan 4 Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan 5 Phalanx Biotech Group, Hsinchu, Taiwan 6 Department of Biotechnology, Ming Chuan University, Taoyuan, Taiwan 7 Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan Correspondence: An-Ning Chao, Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, No. 5 Fuxing St., Guishan District, Taoyuan 333, [Taiwan. e-mail:](Taiwan. e-mail: anning@cgmh.org.tw)[ anning@cgmh.org.tw](Taiwan. e-mail: anning@cgmh.org.tw) Received: July 26, 2025 Accepted: November 4, 2025 Published: December 30, 2025 Keywords: uveal melanoma; low-pass WGS Citation: Huang CY, Wu RC, Chao A, Lin CH, Lin CY, Lee YS, Tsai YJ, Chen KJ, Chao AN. Feasibility of low-pass whole genome sequencing for detecting somatic copy number alterations in formalin-fixed uveal melanoma specimens. Transl Vis Sci Technol. 2025;14(12):31, [https://doi.org/10.1167/tvst.14.12.31](https://doi.org/10.1167/tvst.14.12.31) Purpose: Low-pass whole genome sequencing (LP-WGS), which provides genome-wide coverage ranging from ×0.5 to ×5.0, has recently emerged as a promising tool for identifying chromosomal abnormalities in clinical samples. Here, we sought to investigate the feasibility and clinical utility of LP-WGS in detecting somatic copy number alterations (SCNAs) using formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with uveal melanoma (UM) in an Asian population. Methods: A retrospective study was conducted on 11 Taiwanese patients with UM who underwent enucleation between 2007 and 2021 . Four participants had undergone additional treatment modalities prior to enucleation, including proton therapy (n = 2), external-beam radiation therapy (n = 1), and gamma knife (n = 1) . LP-WGS was performed on DNA extracted from FFPE tissue sections. SCNAs were analyzed in relation to clinical outcomes, and the correlation between monosomy 3 and BAP1 protein expression was investigated. Results: LP-WGS successfully identified SCNAs in nine of 11 (81.8%) tumor specimens, including those from patients who had received treatment before enucleation. Of the two cases yielding noninformative results, one had previously undergone proton therapy. Gain of chromosome 8q, monosomy 3, and loss of chromosome 1p were detected in all five patients who ultimately died of disease. Furthermore, a potential correlation was observed between monosomy 3 and the loss of BAP1 protein expression by immunohistochemistry. Conclusions: LP-WGS appears feasible for SCNAs detection in FFPE uveal melanoma specimens, including cases previously treated before enucleation, and holds promise to inform prognostic stratification in this rare tumor type. Translational Relevance: The successful application of LP-WGS to FFPE uveal melanoma specimens supports prospective investigations in rare cancers and may enable the development of personalized treatment strategies. Copyright 2025 The Authors [tvst.arvojournals.org | ISSN: 2164-2591](tvst.arvojour

FAQs

What was the purpose of using low-pass whole genome sequencing in this study?

To evaluate the feasibility and clinical utility of LP-WGS for detecting somatic copy number alterations in formalin-fixed uveal melanoma tissue samples.

How was the study conducted and who were the participants?

A retrospective study included 11 Taiwanese patients with uveal melanoma who underwent enucleation between 2007 and 2021, with DNA extracted from FFPE tissue sections for LP-WGS analysis.

What key results did the study find?

LP-WGS detected SCNAs in 9 of 11 tumor specimens (81.8%), and monosomy 3 showed a potential correlation with loss of BAP1 protein expression by immunohistochemistry.

Sep 28, 2026

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