Identification of novel fusion transcripts in multiple myeloma
Identification of novel fusion transcripts in multiple myeloma
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多发性骨髓瘤中新型融合转录本的鉴定
DOI：
10.1136/jclinpath-2017-204961
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发表时间：
2018
影响因子：
3.4
通讯作者：
W. Chng
中科院分区：
文献类型：
--
作者：
Mingxuan Lin;Peak;L. Chiu;C. Chua;K. Ban;A. Lin;Zit;Tae;B. Yan;W. Chng
多发性骨髓瘤（MM）是一种异质性疾病，其特征是遗传复杂的异常。经典的突变谱包括复发性染色体畸变和基因水平突变。涉及IGH基因的复发性易位如t（11;14）、t（4;14）和t（14;16）是众所周知的。然而，复杂的遗传异常的存在提出了可能性，融合以外的复发IGH易位存在。因此，我们采用了有针对性的RNA测序面板，以确定新的推定的融合在一个本地队列的MM。方法有针对性的RNA测序进行了21例患者样本使用的Illumina TruSight RNA泛癌症面板（包括1385个基因）。从Illumina RNA测序比对软件（V.1.0.0）生成融合调用。这些样本具有常见复发性染色体异常（t（11;14）、t（4;14）、t（14;16）和17 p13缺失）的常规细胞遗传学和荧光原位杂交数据。使用TopHat-fusion管道分析MMRF CoMMPass数据集。结果TruSight RNA Pan-Cancer Panel共鉴定出10个新融合体。其中两种融合体（HGF/CACNA 2 D 1和SMC 3/MXI 1）通过逆转录PCR和桑格测序进行了验证，因为它们涉及可能与MM发生具有生物学相关性的基因。其中四个（MAP 2K 4/MAP 2K 4P 1）可能是假的，继发于读段与假基因的未对准。从MMRF CoMMPass数据集中鉴定了HGF/CACNA 2D 1融合的一个记录。结论新融合的鉴定为MM的生物学提供了新的见解，并可能具有临床意义。需要进一步的功能研究，以确定这些新的融合的生物学和临床意义。
Aims Multiple myeloma (MM) is a heterogeneous disease characterised by genetically complex abnormalities. The classical mutational spectrum includes recurrent chromosomal aberrations and gene-level mutations. Recurrent translocations involving the IGH gene such as t(11;14), t(4;14) and t(14;16) are well known. However, the presence of complex genetic abnormalities raises the possibility that fusions other than the recurrent IGH translocations exist. We therefore employed a targeted RNA-sequencing panel to identify novel putative fusions in a local cohort of MM. Methods Targeted RNA-sequencing was performed on 21 patient samples using the Illumina TruSight RNA Pan-Cancer Panel (comprising 1385 genes). Fusion calls were generated from the Illumina RNA-Sequencing Alignment software (V.1.0.0). These samples had conventional cytogenetic and fluorescence in situ hybridisation data for the common recurrent chromosomal abnormalities (t(11;14), t(4;14), t(14;16) and 17p13 deletion). The MMRF CoMMpass dataset was analysed using the TopHat-fusion pipeline. Results A total of 10 novel fusions were identified by the TruSight RNA Pan-Cancer Panel. Two of these fusions, HGF/CACNA2D1 and SMC3/MXI1, were validated by reverse transcription PCR and Sanger sequencing as they involve genes that may have biological relevance in MM genesis. Four of these (MAP2K4/MAP2K4P1) are likely to be spurious secondary to misalignment of reads to a pseudogene. One record of the HGF/CACNA2D1 fusion was identified from the MMRF CoMMpass dataset. Conclusions The identification of novel fusions offers insights into the biology of MM and might have clinical relevance. Further functional studies are required to determine the biological and clinical relevance of these novel fusions.
影响因子：
18.4
作者：
Jia Y;Xie Z;Li H
通讯作者：
Li H