Characterization of a cryptic IGH/CCND1 rearrangement in a case of mantle cell lymphoma with negative CCND1 FISH studies

Jess F. Peterson, Linda B. Baughn, Rhett P. Ketterling, Beth A. Pitel, Stephanie A. Smoley, George Vasmatzis, James B. Smadbeck, Patricia T. Greipp, Abhishek A. Mangaonkar, Carrie A. Thompson, Sameer A. Parikh, Dong Chen, David S. Viswanatha

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Mantle cell lymphoma (MCL) is a mature B-cell neoplasm accounting for approximately 3% to 10% of all non-Hodgkin lymphomas.1-3 The molecular hallmark of MCL, t(11;14)(q13;q32) (IGH/CCND1), results in deregulation and overexpression of the G1-phase cell cycle gene, CCND1 (encoding cyclin D1), mediated by enhancer elements found throughout the IGH locus.1-4 The t(11;14) is observed in .95% of MCL cases, with rare reports that describe t(11;14) as being a result of CCND1 and immunoglobulin light chain translocations.1 Cyclin D1-negative MCL resulting from CCND2 or CCND3 rearrangements and immunoglobulin partners highlights the importance of cyclin D overexpression in all MCL subtypes.1,3-6 However, overexpression of cyclin D alone is insufficient to cause MCL, and additional genetic alterations that deregulate cell cycle, DNA damage response, apoptosis, and/or chromatin modifiers are typically required.1-3,7-12 Although cyclin D1 overexpression can occur in other mature B-cell lymphomas such as hairy cell leukemia and rarely chronic lymphocytic leukemia/small lymphocytic lymphoma, IGH/CCND1 fusion detected in mature B-cell lymphomas has been considered diagnostic for MCL.1,13,14 IGH/CCND1 rearrangements are typically detected by fluorescence in situ hybridization (FISH) studies using dual-color dual-fusion (D-FISH) or less commonly by CCND1 break-apart probe sets. We describe a unique case of cyclin D1-positive B-cell lymphoma with partial features of MCL but without CCND1 rearrangement by commercially available FISH probe sets. To further interrogate this discrepancy, a next-generation sequencing (NGS) strategy, mate-pair sequencing (MPseq), was performed, and it revealed a cryptic IGH/CCND1 rearrangement.

Original languageEnglish (US)
Pages (from-to)1298-1302
Number of pages5
JournalBlood Advances
Issue number8
StatePublished - 2019

ASJC Scopus subject areas

  • General Medicine


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