Classifying melanocytic tumors based on DNA copy number changes
Classifying melanocytic tumors based on DNA copy number changes
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DOI：
10.1016/s0002-9440(10)63536-5
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发表时间：
2003-11-01
影响因子：
6
通讯作者：
Pinkel, D
中科院分区：
文献类型：
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作者：
Bastian, BC;Olshen, AB;Pinkel, D
黑色素瘤和良性黑色素细胞痣在组织病理学表现上可以明显重叠，误诊是常见的。为了确定遗传标准是否可以诊断的帮助，我们确定了DNA拷贝数的变化，在186个黑色素细胞肿瘤（132个黑色素瘤和54个良性痣）使用比较基因组杂交。我们发现黑色素瘤和痣之间有非常显著的差异。而127例（96.2%）的黑色素瘤有某种形式的染色体畸变，只有7例（13.0%）的良性痣病例有畸变。所有7例畸变均为斯皮茨痣，其中6例畸变为涉及11号染色体整个短臂的孤立性增益。在132个黑色素瘤中没有观察到这种畸变。我们还分析了132例黑色素瘤的遗传差异，这取决于解剖部位、Clark组织发生类型和阳光照射模式。我们发现，肢端黑色素瘤有显着更多的畸变涉及染色体5p，11q，12q和15，以及集中的基因扩增。黑色素瘤分类为恶性雀斑样痣黑色素瘤或发生在严重晒伤的皮肤显着更频繁的染色体17 p和13 q的损失。这项研究表明，黑色素瘤的染色体畸变模式与黑色素细胞痣不同，应进一步评估作为黑色素细胞病变的诊断试验，目前还不明确。此外，我们显示了黑色素瘤的遗传组成的显着差异，这取决于解剖位置和阳光照射模式，表明潜在的治疗靶点可能会因黑色素瘤类型而异。
Melanoma and benign melanocytic nevi can overlap significantly in their histopathological presentation and misdiagnoses are common. To determine whether genetic criteria can be of diagnostic help we determined DNA copy number changes in 186 melanocytic tumors (132 melanomas and 54 benign nevi) using comparative genomic hybridization. We found highly significant differences between melanomas and nevi. Whereas 127 (96.2%) of the melanomas had some form of chromosomal aberration, only 7 (13.0%) of the benign nevi cases had aberrations. All seven cases with aberrations were Spitz nevi, in six of which the aberration was an isolated gain involving the entire short arm of chromosome 11. This aberration was not observed in any of the 132 melanomas. We also analyzed the 132 melanomas for genetic differences depending on anatomical site, Clark's histogenetic type, and sun-exposure pattern. We show that melanomas on acral sites have significantly more aberrations involving chromosomes 5p, 11q, 12q, and 15, as well as focused gene amplifications. Melanomas classified as lentigo maligna melanomas or as occurring on severely sun-damaged skin showed markedly more frequent losses of chromosomes 17p and 13q. This study shows a pattern of chromosomal aberration in melanoma that is distinct from melanocytic nevi and should be further evaluated as a diagnostic test for melanocytic lesions that are now ambiguous. In addition, we show marked differences in the genetic make-up of melanomas that depend on anatomical location and sun-exposure pattern indicating that potential therapeutic targets might vary among melanoma types.