ホルマリン固定ブドウ膜メラノーマ検体における体細胞コピー数異常検出のための低パス全ゲノムシーケンスの実現可能性

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.

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.

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.

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.

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.