癌症的体细胞进化
不确定意义的单克隆抗体病
生物
多发性骨髓瘤
表观遗传学
遗传异质性
肿瘤微环境
外显子组
肿瘤进展
癌症
比较基因组杂交
外显子组测序
癌症研究
克隆(Java方法)
遗传学
基因组
免疫学
单克隆
突变
单克隆抗体
表型
基因
抗体
作者
Giada Bianchi,Irène M. Ghobrial
出处
期刊:Current Cancer Therapy Reviews
[Bentham Science]
日期:2014-11-24
卷期号:10 (2): 70-79
被引量:33
标识
DOI:10.2174/157339471002141124121404
摘要
Clonal heterogeneity and clonal evolution have emerged as critical concepts in the field of oncology over the past four decades, largely thanks to the implementation of novel technologies such as comparative genomic hybridization, whole genome/exome sequencing and epigenetic analysis. Along with the identification of cancer stem cells in the majority of neoplasia, the recognition of intertumor and intratumor variability has provided a novel perspective to understand the mechanisms behind tumor evolution and its implication in terms of treatment failure and cancer relapse or recurrence. First hypothesized over two decades ago, clonal heterogeneity and clonal evolution have been confirmed in multiple myeloma (MM), an incurable cancer of plasma cells, almost universally preceded by a pre-malignant conditioned named monoclonal gammopathy of undetermined significance (MGUS). The genetic events and molecular mechanisms underlying such evolution have been difficult to dissect. Moreover, while a role for the bone marrow microenvironment in supporting MM cell survival, proliferation and drug-resistance has been well established, whether it is directly involved in driving evolution from MGUS to MM is at present unclear. We present in this review a historical excursus on the concepts of clonal heterogeneity and clonal evolution in MM with a special emphasis on their role in the progression from MGUS to MM; the contribution of the microenvironment; and the clinical implications in terms of resistance to treatment and disease relapse/recurrence.
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