伴有新型t(11;12)(q13;p11.2)的套细胞淋巴瘤：CCND1上调的一种可能替代机制
Mantle cell lymphoma with a novel t(11;12)(q13;p11.2): a proposed alternative mechanism of CCND1 up-regulation.
作者信息
Menke Joshua R, Vasmatzis George, Murphy Stephen, Yang Lin, Menke David M, Tun Han W, King Rebecca L, Smoley Stephanie A, Ketterling Rhett P, Sukov William R
机构信息
Department of Pathology, University of California, San Francisco, CA 94143.
Center for Individualized Medicine, Mayo Clinic, Rochester MN 55905.
出版信息
Hum Pathol. 2017 Jun;64:207-212. doi: 10.1016/j.humpath.2017.01.001. Epub 2017 Jan 27.
Mantle cell lymphoma (MCL) is typically characterized by t(11;14), which places the IGH@ enhancer elements upstream of CCND1. This fusion results in up-regulation of CCND1 and consequently its protein product cyclin D1. Recent studies have shown that in MCL, mutations or translocations occurring within the 3' untranslated region (UTR) of the CCND1 gene can result in a truncated mRNA transcript that is more stable and associated with more aggressive disease. We identified a case of MCL showing cyclin D1 overexpression by immunohistochemistry and a t(11;12)(q13;p11.2) by conventional cytogenetic studies. Next-generation genomic sequencing indicated a chromosomal break through the CCND1 3'-UTR and fusion with a non-coding region of chromosome 12. We suggest that, in the absence of the typical CCND1/IGH@ fusion, this rearrangement promotes MCL pathogenesis by eliminating miRNA interaction elements within the 3'-UTR of the CCND1 mRNA transcript consequently resulting in CCND1 overexpression.
套细胞淋巴瘤（MCL）的典型特征是t(11;14)，该异常使IGH@增强子元件位于CCND1上游。这种融合导致CCND1上调，进而导致其蛋白产物细胞周期蛋白D1上调。最近的研究表明，在MCL中，CCND1基因3'非翻译区（UTR）内发生的突变或易位可导致截短的mRNA转录本，其更稳定且与侵袭性更强的疾病相关。我们通过免疫组织化学鉴定了1例显示细胞周期蛋白D1过表达且通过传统细胞遗传学研究发现t(11;12)(q13;p11.2)的MCL病例。下一代基因组测序表明存在一条贯穿CCND1 3'-UTR的染色体断裂，并与12号染色体的一个非编码区融合。我们认为，在不存在典型的CCND1/IGH@融合的情况下，这种重排通过消除CCND1 mRNA转录本3'-UTR内的miRNA相互作用元件促进MCL发病机制，从而导致CCND1过表达。
Zotero 插件