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Copy Number Variation in Archival Melanoma Biopsies versus Benign Melanocytic Lesions

机译:档案黑色素瘤活检与良性黑色素细胞病变的拷贝数变化

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摘要

BACKGROUND: Skin melanocytes can give rise to benign and malignant neoplasms. Discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. However, previous studies have shown that in contrast to benign nevi, melanoma demonstrates pervasive chromosomal aberrations. OBJECTIVE: This substantial difference between melanoma and benign nevi can be exploited to discriminate between melanoma and benign nevi. METHODS: Array-comparative genomic hybridization (aCGH) is an approach that can be used on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues to assess the entire genome for the presence of changes in DNA copy number. In this study, high resolution, genome-wide single-nucleotide polymorphism (SNP) arrays were utilized to perform comprehensive and detailed analyses of recurrent copy number aberrations in 41 melanoma samples in comparison with 21 benign nevi. RESULTS: We found statistically significant copy number gains and losses within melanoma samples. Some of the identified aberrations are previously implicated in melanoma. Moreover, novel regions of copy number alterations were identified, revealing new candidate genes potentially involved in melanoma pathogenesis. CONCLUSIONS: Taken together, these findings can help improve melanoma diagnosis and introduce novel melanoma therapeutic targets.
机译:背景:皮肤黑素细胞可引起良性和恶性肿瘤。从不正常/非典型良性痣中鉴别出早期黑色素瘤可能是一个重大挑战。但是,先前的研究表明,与良性痣相反,黑色素瘤表现出普遍的染色体畸变。目的:黑色素瘤和良性痣之间的实质性区别可以用来区分黑色素瘤和良性痣。方法:阵列比较基因组杂交(aCGH)是一种可用于从福尔马林固定石蜡包埋(FFPE)组织提取的DNA上评估整个基因组DNA拷贝数变化的方法。在这项研究中,高分辨率的全基因组单核苷酸多态性(SNP)阵列被用来对41个黑色素瘤样品与21个良性痣进行比较,对循环拷贝数畸变进行全面而详细的分析。结果:我们发现黑色素瘤样本中具有统计学意义的拷贝数增减。某些识别出的像差先前与黑色素瘤有关。此外,鉴定了新的拷贝数改变区域,揭示了潜在地涉及黑素瘤发病机理的新候选基因。结论:综上所述,这些发现可以帮助改善黑色素瘤的诊断并引入新的黑色素瘤治疗靶标。

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