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Genomic analysis of metastatic melanoma in an adult with giant congenital melanocytic nevus.
Pigment Cell & Melanoma Research ( IF 4.3 ) Pub Date : 2020-02-24 , DOI: 10.1111/pcmr.12872
Li-Wei Chang 1 , Ramiz Iqbal 2 , Brateil Badal 2 , Daniel Bernstein 3 , Karen Mendelson 2 , Alexander Solovyov 2, 4, 5, 6 , Philip Friedlander 4, 5 , Robert Phelps 2, 3 , Herbert Goodheart 3 , Garrett Desman 2 , Benjamin D Greenbaum 2, 4, 5, 6 , Julide Tok Celebi 2, 3, 4, 6
Affiliation  

Giant congenital melanocytic nevi (GCMN) are benign cutaneous lesions associated with increased risk for developing melanoma. Genomic studies of congenital melanocytic nevi revealed NRAS mutation as the sole mutational event in these lesions. However, studies to date have focused on mutations of benign lesions but not the malignant counterparts. Here, we performed genomic analysis of metastatic melanoma in a patient with a GCMN. We used whole exome sequencing to confirm an identical NRASQ61R mutation in the GCMN and the metastatic tumor in the lung. We identified additional somatic mutations in the metastatic tumor that may have contributed to the malignant transformation and metastasis. Gene expression analysis comparing this patient's GCMN with NRAS‐mutant melanoma from the Cancer Genome Atlas (TCGA) characterized dysregulated genes including tumor suppressors and those involved in development, cell fate determination, and stem cell pluripotency. Our results support further molecular and functional studies of melanoma arising in GCMN using matched benign and malignant samples from the same patients. Studying this distinct melanoma subset may shed light on the benign to malignant transformation and metastasis of NRAS‐driven tumors.

中文翻译:

成人巨大先天性黑素细胞痣的转移性黑色素瘤的基因组分析。

巨大的先天性黑素细胞痣(GCMN)是皮肤良性病变,与发展黑色素瘤的风险增加有关。先天性黑素细胞痣的基因组研究表明,NRAS突变是这些病变中唯一的突变事件。然而,迄今为止的研究集中于良性病变的突变,而不是恶性病变。在这里,我们对患有GCMN的患者进行了转移性黑色素瘤的基因组分析。我们使用整个外显子组测序来确认GCMN中相同的NRAS Q61R突变和肺部转移性肿瘤。我们在转移性肿瘤中发现了额外的体细胞突变,这些突变可能导致了恶性转化和转移。比较该患者的GCMN和NRAS的基因表达分析来自癌症基因组图谱(TCGA)的突变型黑色素瘤表现出失调的基因,包括抑癌基因以及参与发育,细胞命运确定和干细胞多能性的基因。我们的结果支持使用来自相同患者的匹配的良性和恶性样本对GCMN中产生的黑色素瘤进行进一步的分子和功能研究。研究这种独特的黑色素瘤子集可能有助于阐明NRAS驱动的肿瘤的良性到恶性转化和转移。
更新日期:2020-02-25
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