Mantle cell lymphoma with a novel t(11;12)(q13;p11.2): A proposed alternative mechanism of CCND1 upregulation

Publication date: Available online 27 January 2017
Source:Human Pathology
Author(s): Joshua R. Menke, George Vasmatzis, Stephen Murphy, Lin Yang, David M. Menke, Han W. Tun, Rebecca L. King, Stephanie A. Smoley, Rhett P. Ketterling, William R. Sukov
Mantle cell lymphoma (MCL) is typically characterized by t(11;14) which places the IGH@ enhancer elements upstream of CCND1. This fusion results in upregulation 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.



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