Liverpool Ocular Oncology Research Group, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Aintree University Hospital, Liverpool, UK.
Pigment Cell Melanoma Res. 2019 Jul;32(4):564-575. doi: 10.1111/pcmr.12767. Epub 2019 Feb 19.
Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.
关于结膜黑色素瘤(CoM)的遗传异常及其与临床和组织形态学特征以及预后的相关性,人们知之甚少。本大型合作多中心研究的目的是确定转移性风险的潜在关键生物标志物,以及高转移性风险 CoM 的潜在治疗靶点。我们使用 Affymetrix 单核苷酸多态性基因分型阵列对 59 例 CoM 进行检测,发现染色体 6p 频繁扩增和 7q 缺失,并对突变特异性拷贝数改变进行了特征描述。10q11.21-26.2 染色体上的缺失,该区域包含肿瘤抑制基因 PDCD4、SUFU、NEURL1、PTEN、RASSF4、DMBT1、C10orf90 和 C10orf99,与转移(Fisher 精确检验,p≤0.04)、淋巴浸润(Fisher 精确检验,p≤0.02)、肿瘤厚度增加(Mann-Whitney,p≤0.02)和 BRAF 突变(Fisher 精确检验,p≤0.05)显著相关。这一深入了解 CoM 生物学的研究是朝着确定具有转移风险的患者和全身疾病的潜在治疗靶点迈出的一步。