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

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

Research output: Contribution to journalArticle

Abstract

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
Volume3
Issue number8
DOIs
StatePublished - Jan 1 2019

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Mantle-Cell Lymphoma
Cyclin D1
Fluorescence In Situ Hybridization
B-Cell Lymphoma
Cyclin D
B-Cell Chronic Lymphocytic Leukemia
Immunoglobulin Light Chains
Hairy Cell Leukemia
cdc Genes
G1 Phase
Non-Hodgkin's Lymphoma
DNA Damage
Chromatin
Immunoglobulins
Cell Cycle
B-Lymphocytes
Color

ASJC Scopus subject areas

  • Medicine(all)

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Characterization of a cryptic IGH/CCND1 rearrangement in a case of mantle cell lymphoma with negative CCND1 FISH studies. / Peterson, Jess F.; Baughn, Linda; Ketterling, Rhett P.; Pitel, Beth A.; Smoley, Stephanie A.; Vasmatzis, George; Smadbeck, James; Greipp, Patricia T; Mangaonkar, Abhishek A.; Thompson, Carrie A.; Parikh, Sameer A; Chen, Dong; Viswanatha, David S.

In: Blood Advances, Vol. 3, No. 8, 01.01.2019, p. 1298-1302.

Research output: Contribution to journalArticle

Peterson, Jess F. ; Baughn, Linda ; Ketterling, Rhett P. ; Pitel, Beth A. ; Smoley, Stephanie A. ; Vasmatzis, George ; Smadbeck, James ; Greipp, Patricia T ; Mangaonkar, Abhishek A. ; Thompson, Carrie A. ; Parikh, Sameer A ; Chen, Dong ; Viswanatha, David S. / Characterization of a cryptic IGH/CCND1 rearrangement in a case of mantle cell lymphoma with negative CCND1 FISH studies. In: Blood Advances. 2019 ; Vol. 3, No. 8. pp. 1298-1302.
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AU - Baughn, Linda

AU - Ketterling, Rhett P.

AU - Pitel, Beth A.

AU - Smoley, Stephanie A.

AU - Vasmatzis, George

AU - Smadbeck, James

AU - Greipp, Patricia T

AU - Mangaonkar, Abhishek A.

AU - Thompson, Carrie A.

AU - Parikh, Sameer A

AU - Chen, Dong

AU - Viswanatha, David S.

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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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