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多发性骨髓瘤中的基因组畸变

Genomic Aberrations in Multiple Myeloma.

作者信息

Manier Salomon, Salem Karma, Glavey Siobhan V, Roccaro Aldo M, Ghobrial Irene M

机构信息

Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.

Department of Hematology, Lille Hospital University, Lille, France.

出版信息

Cancer Treat Res. 2016;169:23-34. doi: 10.1007/978-3-319-40320-5_3.

Abstract

Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes. HRD tumors are characterized by trisomy of chromosomes 3, 5, 7, 9, 11, 15, 19, and/or 21. Non-HRD tumors harbor IGH translocations, mainly t(4;14), t(6;14), t(11;14), t(14;16), and t(14;20). Secondary events participate to the tumor progression and consist in secondary translocation involving MYC, copy number variations (CNV) and somatic mutations (such as mutations in KRAS, NRAS, BRAF, P53). Moreover, the dissection of clonal heterogeneity helps to understand the evolution of the disease. The following review provides a comprehensive review of the genomic landscape in MM.

摘要

多发性骨髓瘤(MM)是一种基因复杂的疾病。过去几年,随着下一代测序(NGS)的出现,癌症研究取得了进展,NGS能够对肿瘤进行高通量测序,包括全外显子组、全基因组、RNA和单细胞测序以及全基因组关联研究(GWAS)。已经描述了一些遗传变异,解释了部分家族性疾病病例。从层次上讲,MM的主要事件可分为超二倍体(HDR)和非超二倍体亚型。HDR肿瘤的特征是染色体3、5、7、9、11、15、19和/或21三体。非HDR肿瘤存在IGH易位,主要是t(4;14)、t(6;14)、t(11;14)、t(14;16)和t(14;20)。继发性事件参与肿瘤进展,包括涉及MYC的继发性易位、拷贝数变异(CNV)和体细胞突变(如KRAS、NRAS、BRAF、P53中的突变)。此外,克隆异质性的剖析有助于理解疾病的演变。以下综述全面回顾了MM的基因组格局。

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