Clonal persistence and evolution during a decade of recurrent melanoma.

Clonal persistence and evolution during a decade of recurrent melanoma.
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十年来复发性黑色素瘤的克隆持久性和进化。

DOI:
10.1038/sj.jid.5700193
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发表时间:
2006
期刊:
The Journal of investigative dermatology.
影响因子:
--
通讯作者:
Marincola,FrancescoM
Marincola,FrancescoM
中科院分区:
--
文献类型:
--
作者:
Wang,Ena;Voiculescu,Sonia;LePoole,IsabelleC;El-Gamil,Mona;Li,Xin;Sabatino,Marianna;Robbins,PaulF;Nickoloff,BrianJ;Marincola,FrancescoM

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一名对免疫治疗有反应的转移性皮肤黑色素瘤患者在十年的观察中经历了多次复发。每次复发时,都会获得活组织检查并生成细胞系。所有细胞系中都记录了β-连环蛋白基因的罕见突变和雄激素受体的不平衡甲基化。尽管表型不同,但核型分析和比较基因组杂交鉴定出一致的遗传特征,这表明所有转移瘤均源自同一原发性肿瘤,尽管它们可能并非以连续方式源自最近的先前转移瘤。因此,转移性黑色素瘤由共同祖细胞复发,并且表型变化发生在遗传稳定性的核心周围。这一观察结果可能对靶向抗癌疗法的开发具有重要意义。
A patient with metastatic cutaneous melanoma responsive to immunotherapy experienced several recurrences over a decade of observation. With each recurrence, biopsies were obtained and cell lines generated. A rare mutation of theβ-catenin gene and an unbalanced methylation of the androgen receptor were documented in all cell lines. Karyotyping and comparative genomic hybridization identified consistent genetic traits in spite of divergent phenotypes, suggesting that all the metastases were derived from the same primary tumor, although they were each probably not derived from the most recent previous metastasis in a sequential manner. Thus, metastatic melanoma recurs from a common progenitor cell and phenotypic changes occur around a central core of genetic stability. This observation may bear significance for the development of targeted anticancer therapies.
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DOI: --
发表时间: 1995
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