Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida
JAMA Ophthalmol. 2017 Dec 1;135(12):1434-1437. doi: 10.1001/jamaophthalmol.2017.4837.
Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood.
To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES).
DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline.
Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures.
The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p.
In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.
结膜黑色素瘤（CM）是一种高度侵袭性的眼部癌症，其治疗选择有限；其分子发病机制知之甚少。
使用下一代全外显子组测序（WES）鉴定 CM 的分子特征。
设计、设置和参与者：对 2006 年至 2011 年间接受手术切除治疗的 5 例 CM 患者的存档标本中提取的肿瘤 DNA 进行全外显子组测序。这些样本在三级学术眼科肿瘤转诊中心使用定制的生物信息学管道进行分析。
样本分析旨在检测驱动突变、染色体拷贝数异常和突变特征。
本研究的 5 名患者年龄在 51 岁至 77 岁之间。5 名患者中有 4 名女性，均为白人。在已知的致癌基因中检测到突变，包括 BRAF、NRAS、NF1、EGFR、ALK、TERT 和 APC。未发现与葡萄膜黑色素瘤相关的突变。所有样本均表现出与 UV 诱导的 DNA 损伤相关的 C→T 突变特征。最常见的 CNA 是 6p 染色体增益。
在这 5 名患者中，WES 允许鉴定可通过治疗靶向的突变，并支持 UV 光在 CM 发病机制中的作用。这些发现表明需要更大的研究来评估 WES 对 CM 的诊断、预后和治疗价值。
