Differential RNA splicing as a potentially important driver mechanism in multiple myeloma.
Differential RNA splicing as a potentially important driver mechanism in multiple myeloma.
复制标题
DOI：
10.3324/haematol.2019.235424
复制
发表时间：
2021-03-01
期刊：
影响因子：
10.1
通讯作者：
Walker BA
中科院分区：
文献类型：
--
作者：
Bauer MA;Ashby C;Wardell C;Boyle EM;Ortiz M;Flynt E;Thakurta A;Morgan G;Walker BA
RNA正常剪接模式的破坏是许多疾病发生的主要因素。越来越多的研究表明，剪接模式对癌症进展有很大的影响。多发性骨髓瘤是一种分子异质性疾病，根据关键易位、基因表达谱和突变的存在进行分类，但MM中的剪接模式在很大程度上仍未探索。我们采取多方面的方法来定义MM中选择性剪接的程度和影响。我们研究了剪接体组分SF 3B 1，热点突变（K700 E和K666 T/Q）显示会导致其他癌症中选择性剪接的增加。我们在SF 3B 1突变体和野生型样品的比较中发现了许多差异剪接的基因，包括MZB 1、DYNLL 1、TMEM 14 C和剪接相关基因DHX 9、CLASRP和SNRPE。我们确定了一个更广泛的作用，异常剪接显示出明显的差异，在不同的易位组中的新的剪接变异体的程度。我们发现大量的新剪接位点与不良生存率和超高风险组相关。选择性剪接模式的列举有可能细化MM分类，并有助于患者的风险分层。
Disruption of the normal splicing patterns of RNA is a major factor in the path o genesis of a number of diseases. Increasingl y research has shown the strong influence that splicing patterns can have on cancer progression. Multiple myeloma is a molecularly heterogeneous disease classified by the presence of key translocations, gene expression profiles and mutations but the splicing patterns in MM remains largely unexplored. We take a multifaceted approach to define the extent and impact of alternative splicing in MM. We looked at the spliceosome component, SF3B1, with hotspot mutations (K700E and K666T/Q) shown to result in an increase in alternative splicing in other cancers. We discovered a number of differentially spliced genes in comparison of the SF3B1 mutant and wild type samples that included, MZB1, DYNLL1, TMEM14C and splicing related genes DHX9, CLASRP, and SNRPE. We identified a broader role for abnormal splicing showing clear differences in the extent of novel splice variants in the different translocation groups. We show that a high number of novel splice loci is associated with adverse survival and an ultra-high risk group. The enumeration of patterns of alternative splicing has the potential to refine MM classification and to aid in the risk stratification of patients.
登录
查看更多内容
影响因子：
4.3
作者：
Corvelo A;Hallegger M;Smith CW;Eyras E
通讯作者：
Eyras E
影响因子：
50.3
作者：
Obeng EA;Chappell RJ;Seiler M;Chen MC;Campagna DR;Schmidt PJ;Schneider RK;Lord AM;Wang L;Gambe RG;McConkey ME;Ali AM;Raza A;Yu L;Buonamici S;Smith PG;Mullally A;Wu CJ;Fleming MD;Ebert BL
通讯作者：
Ebert BL
建模癌症中的SF3B1突变：进步，挑战和机遇。
影响因子：
50.3
作者：
Inoue D;Abdel-Wahab O
通讯作者：
Abdel-Wahab O
影响因子：
8
作者：
Kesarwani AK;Ramirez O;Gupta AK;Yang X;Murthy T;Minella AC;Pillai MM
通讯作者：
Pillai MM
DOI：
10.1002/path.4483
发表时间：
2015-03
期刊：
The Journal of pathology
影响因子：
--
作者：
Maguire SL;Leonidou A;Wai P;Marchiò C;Ng CK;Sapino A;Salomon AV;Reis-Filho JS;Weigelt B;Natrajan RC
通讯作者：
Natrajan RC