TY - JOUR
T1 - Characterization of a cryptic IGH/CCND1 rearrangement in a case of mantle cell lymphoma with negative CCND1 FISH studies
AU - Peterson, Jess F.
AU - Baughn, Linda B.
AU - Ketterling, Rhett P.
AU - Pitel, Beth A.
AU - Smoley, Stephanie A.
AU - Vasmatzis, George
AU - Smadbeck, James B.
AU - Greipp, Patricia T.
AU - Mangaonkar, Abhishek A.
AU - Thompson, Carrie A.
AU - Parikh, Sameer A.
AU - Chen, Dong
AU - Viswanatha, David S.
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2019031450
DO - 10.1182/bloodadvances.2019031450
M3 - Article
C2 - 31015206
AN - SCOPUS:85068626556
SN - 2473-9529
VL - 3
SP - 1298
EP - 1302
JO - Blood Advances
JF - Blood Advances
IS - 8
ER -