Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion
Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion
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DOI：
10.1111/j.1365-2133.2007.07924.x
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发表时间：
2007-06-01
影响因子：
10.3
通讯作者：
Saida, T.
中科院分区：
文献类型：
--
作者：
Takata, M.;Lin, J.;Saida, T.
背景恶性黑色素瘤和Spitz痣的组织病理学鉴别常常提出诊断问题。目的我们的目的是找出适用的诊断参数以外的常规pathology.Methods的情况下，包括传统的黑色素瘤和Spitz痣以及不典型的spitzoid病变，造成诊断困难。我们通过基于聚合酶链反应的直接测序检测了BRAF、NRAS和HRAS基因的突变热点。我们还分析了DNA拷贝数畸变和甲基化的CpG序列在几个癌症相关的基因，通过利用一种新的甲基化特异性多重连接依赖探针amplifiedmethod.Results二十三个24个传统的黑色素瘤表现出至少一个遗传和表观遗传学的改变检查，虽然一个肢端黑色素瘤没有表现出任何改变。与此形成鲜明对比的是，12例Spitz痣的组织病理学明确，没有或很少染色体畸变，没有癌基因突变，没有甲基化的CpG序列。在16个不明确的斯皮茨样病变中，其中大部分被一位作者指定为非典型斯皮茨瘤，除一个外，所有病变均未显示突变、甲基化和少量拷贝数畸变。然而，三个肿瘤表现出细胞周期蛋白依赖性激酶抑制剂2A基因（CDKN2A）的拷贝数丢失，这种改变在黑色素瘤中经常观察到，但在传统的斯皮茨痣中没有发现。这些结果表明，虽然大多数非典型施皮茨瘤没有什么不同，从传统的施皮茨痣显示几乎没有遗传和表观遗传畸变，有些情况下可能有染色体畸变，包括拷贝数丢失的CDKN2A基因。结论遗传和表观遗传分析可能是有用的，作为一个额外的诊断工具，以区分黑色素瘤和施皮茨痣，并可能有助于定义亚组在非典型施皮茨瘤。
Background The histopathological differentiation of malignant melanoma and Spitz naevus often presents diagnostic problems.Objectives We aimed to find out applicable diagnostic parameters other than routine pathology.Methods The cases included conventional melanomas and Spitz naevi as well as atypical spitzoid lesions that had posed diagnostic difficulties. We examined hotspots of mutation in the BRAF, NRAS and HRAS genes by polymerase chain reaction-based direct sequencing. We also analysed DNA copy number aberrations and the methylation of CpG sequences in several cancer-related genes by utilizing a novel methylation-specific multiplex ligation-dependent probe amplification method.Results Twenty three of 24 conventional melanomas showed at least one of the genetic and epigenetic alterations examined, although one acral melanoma did not show any alteration. By sharp contrast, 12 Spitz naevi with an unambiguous histopathology showed no or few chromosomal aberrations, no oncogene mutations and no methylation of CpG sequences. Of the 16 ambiguous spitzoid lesions, most of which were designated atypical Spitz tumour by one of the authors, all but one showed no mutations, no methylations and few copy number aberrations. However, three tumours showed copy number loss of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), an alteration observed frequently in melanomas but not found in conventional Spitz naevi. These results show that, although most atypical Spitz tumours do not differ from conventional Spitz naevi showing virtually no genetic and epigenetic aberrations, some cases may have chromosomal aberrations that include copy number loss of the CDKN2A gene.Conclusions Genetic and epigenetic analyses may be useful as an additional diagnostic tool to distinguish between melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz tumours.