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转移性原发性葡萄膜黑色素瘤中3号染色体的伴随性缺失以及1号、6号或8号染色体的整条臂的缺失和增加。

Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma.

作者信息

Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S

机构信息

Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Finland.

出版信息

Invest Ophthalmol Vis Sci. 2001 Feb;42(2):313-7.

PMID:11157859

Abstract

PURPOSE

To elucidate the genetic differences between metastasizing and nonmetastasizing primary tumors, uveal melanoma samples were screened for DNA copy number alterations by comparative genomic hybridization (CGH).

METHODS

DNA copy number changes were studied on 14 primary uveal melanomas that had not metastasized, 15 primary uveal melanomas that had metastasized, and on 6 metastases that were available from 6 primary uveal melanomas. CGH is based on quantitation of the fluorescence intensity of differentially labeled DNAs. Tumor DNA labeled with FITC dCTP and dUTP and normal DNA labeled with Texas red dCTP and dUTP were hybridized to normal metaphase chromosomes. The hybridizations were analyzed using an Olympus fluorescence microscope and the ISIS digital image analysis system to identify gain or loss of genetic material.

RESULTS

Primary uveal melanomas that had metastasized and metastases had significantly more changes than primary uveal melanomas that had not metastasized. Comparison between primary nonmetastasizing tumors, metastasizing tumors, and metastases showed that the most common DNA copy number changes were -3 (21%, 73%, 67%, respectively), -6q (7%, 40%, 83%), -1p (0, 33%, 33%), -13q (14%, 13%, 50%), -8p (14%, 27%, 0), -18 (7%, 13%, 33%), +8q (14%, 53%, 100%), +6p (29%, 20%, 17%), +1q (0, 7%, 33%), and +16p (0, 7%, 33%).

CONCLUSIONS

Loss of chromosome 3, loss of 6q, and gain of 8q were significantly associated with poor overall survival. In addition, losses of 1p were only found in primary uveal melanomas that had metastasized and in metastases, which suggests that this region may harbor a tumor suppressor gene important in the tumor progression. Finally, loss of chromosome 3 may be associated with isochromosome formation of 1q, 6p, 8q, 16p, 20q, and 22q.

摘要

目的

为阐明转移性和非转移性原发性肿瘤之间的基因差异，采用比较基因组杂交（CGH）技术对葡萄膜黑色素瘤样本进行DNA拷贝数改变的筛查。

方法

对14例未发生转移的原发性葡萄膜黑色素瘤、15例已发生转移的原发性葡萄膜黑色素瘤以及来自6例原发性葡萄膜黑色素瘤的6个转移灶进行DNA拷贝数变化研究。CGH基于对差异标记DNA荧光强度的定量分析。用FITC dCTP和dUTP标记的肿瘤DNA以及用Texas red dCTP和dUTP标记的正常DNA与正常中期染色体进行杂交。使用奥林巴斯荧光显微镜和ISIS数字图像分析系统对杂交结果进行分析，以确定遗传物质的增减。

结果

已发生转移的原发性葡萄膜黑色素瘤及其转移灶的变化明显多于未发生转移的原发性葡萄膜黑色素瘤。对原发性非转移性肿瘤、转移性肿瘤和转移灶进行比较发现，最常见的DNA拷贝数变化为-3（分别为21%、73%、67%）、-6q（7%、40%、83%）、-1p（0、33%、33%）、-13q（14%、13%、50%）、-8p（14%、27%、0）、-18（7%、13%、33%）、+8q（14%、53%、100%）、+6p（29%、20%、17%）、+1q（0、7%、33%）和+16p（0、7%、33%）。