Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, BC, Canada V5Z 1L3.
Blood. 2013 Apr 18;121(16):3161-4. doi: 10.1182/blood-2013-01-478834. Epub 2013 Feb 13.
We have recently reported the application of RNAseq to mantle cell lymphoma (MCL) transcriptomes revealing recurrent mutations in NOTCH1. Here we describe the targeted resequencing of 18 genes mutated in this discovery cohort using a larger cohort of MCL tumors. In addition to frequent mutations in ATM, CCND1, TP53, and NOTCH1, mutations were also observed recurrently in MEF2B, TRAF2, and TET2. Interestingly, the third most frequently mutated gene was UBR5, a gene encoding a 2799aa protein, with multiple functions, including E3 ligase activity based on a conserved cysteine residue at the C-terminus. Nonsynonymous mutations were detected in 18% (18/102) of tumors, with 61% of the mutations resulting in frameshifts in, or around, exon 58, predicted to result in the loss of this conserved cysteine residue. The recurrence and clustering of deleterious mutations implicate UBR5 mutations as a critical pathogenic event in a subgroup of MCL.
我们最近报道了 RNAseq 在套细胞淋巴瘤 (MCL) 转录组中的应用，揭示了 NOTCH1 中的反复突变。在这里，我们使用更大的 MCL 肿瘤队列描述了在该发现队列中发生突变的 18 个基因的靶向重测序。除了 ATM、CCND1、TP53 和 NOTCH1 中的频繁突变外，MEF2B、TRAF2 和 TET2 中的突变也经常发生。有趣的是，第三大经常突变的基因是 UBR5，它编码一个具有多种功能的 2799aa 蛋白，包括基于 C 末端保守半胱氨酸残基的 E3 连接酶活性。在 18%（18/102）的肿瘤中检测到非同义突变，其中 61%的突变导致外显子 58 内或周围的移码，预计会导致该保守半胱氨酸残基的丢失。有害突变的重现和聚类表明 UBR5 突变是 MCL 亚组中的一个关键致病事件。
