Whole genome sequencing demonstrates substantial pathophysiological differences of MYC rearrangements in patients with plasma cell myeloma and B-cell lymphoma

Abstract Abstract 4633 Background: Golgins are proteins of the Golgi complex. Several Golgins have been implicated in apoptosis. Expression of Golgin-84, a Golgin protein, is altered in apoptotic WEHI-231, a B-cell lymphoma line, suggesting that Golgin-84 may play a role in lymphoid tumorigenesis. Here, we aimed to determine the expression levels of Golgin-84 in human primary non-Hodgkin lymphomas and plasma cell myeloma. Design: Golgin-84 expression was investigated in non-Hodgkin lymphoma cell lines by using Western blot analysis and polyclonal antibodies. Using immunohistochemical stains, Western blotting analysis and Q-PCR, Golgin-84 expression was assessed in 5 reactive lymph nodes, 149 cases of primary non-Hodgkin lymphoma and 28 cases of primary plasma cell myeloma. Results: Immunohistochemical stains, Western blotting analysis and Q-PCR on 5 reactive lymph nodes demonstrated that Golgin-84 was expressed at low levels in lymphoid cells of germinal centers, mantle cells, marginal zones, and interfollicular areas. Golgin-84 was variably expressed in non-Hodgkin lymphoma cell lines tested, with the highest levels in cells from high-grade tumors (e.g. anaplastic large cell lymphoma; ALCL, Diffuse large B-cell lymphoma (DLBCL), ALCL and peripheral T-cell lymphoma unspecified (PTCL)) and the lowest levels in mantle cell lymphoma (MCL) cells. DLBCL, ALCL and PTCL frequently showed high expression of Golgin-84. Most lymphoplasmacytic lymphomas (LPL) and plasma cell myeloma (PCM) expressed high levels of Golgin-84. Expression levels of Golgin-84 were lower in MCL and low-grade B-cell non-Hodgkin lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Conclusions: Golgin-84 expression levels are low in lymphoid cells of normal lymph nodes. Most (>90%) cases of LPL and PCM, and at least half of cases of DLBCL, ALCL and PTCL express high levels of Golgin-84. These findings suggest that Golgin-84 may be involved in tumorigenesis or lymphoma progression, particularly in neoplasms with plasmacytic differentiation. Disclosures: No relevant conflicts of interest to declare.

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Immunophenotypic Differentiation Between Neoplastic Plasma Cells in Mature B-Cell Lymphoma vs Plasma Cell Myeloma

American Journal of Clinical Pathology ◽

10.1309/5el22bh45phupm8p ◽

2007 ◽

Vol 127 (2) ◽

pp. 176-181 ◽

Cited By ~ 65

Author(s):

Adam C. Seegmiller ◽

Yin Xu ◽

Robert W. McKenna ◽

Nitin J. Karandikar

Keyword(s):

B Cell ◽

Plasma Cell ◽

Plasma Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Plasma Cell Myeloma

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A Common Clonal Origin of Nodal Marginal Zone B-Cell Lymphoma and Plasma Cell Myeloma Demonstrating Different Immunophenotypes

Diagnostic Molecular Pathology ◽

10.1097/00019606-200406000-00003 ◽

2004 ◽

Vol 13 (2) ◽

pp. 75-80 ◽

Cited By ~ 8

Author(s):

Hajime Saito ◽

Kuniyuki Oka ◽

Naoya Nakamura ◽

Reizo Nagayama ◽

Hando Hakozaki ◽

...

Keyword(s):

B Cell ◽

Plasma Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Plasma Cell Myeloma ◽

Clonal Origin

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Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma

Scientific Reports ◽

10.1038/s41598-021-85354-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hannah E. Roberts ◽

Maria Lopopolo ◽

Alistair T. Pagnamenta ◽

Eshita Sharma ◽

Duncan Parkes ◽

...

Keyword(s):

B Cell ◽

Genome Sequencing ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Somatic Variation ◽

Single Nucleotide Variants ◽

Germline Variants ◽

Specificity And Sensitivity ◽

Long Reads ◽

Long Read

AbstractRecent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.

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Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype

Haematologica ◽

10.3324/haematol.2009.016113 ◽

2010 ◽

Vol 95 (8) ◽

pp. 1342-1349 ◽

Cited By ~ 82

Author(s):

S. Montes-Moreno ◽

A.-R. Gonzalez-Medina ◽

S.-M. Rodriguez-Pinilla ◽

L. Maestre ◽

L. Sanchez-Verde ◽

...

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Plasma Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Plasmablastic Lymphoma ◽

Plasma Cell Differentiation ◽

Large B Cell Lymphoma ◽

Large B Cell

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Machine learning enables detection of early-stage colorectal cancer by whole-genome sequencing of plasma cell-free DNA

BMC Cancer ◽

10.1186/s12885-019-6003-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 10

Author(s):

Nathan Wan ◽

David Weinberg ◽

Tzu-Yu Liu ◽

Katherine Niehaus ◽

Eric A. Ariazi ◽

...

Keyword(s):

Colorectal Cancer ◽

Machine Learning ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Plasma Cell ◽

Early Stage ◽

Whole Genome ◽

Cell Free Dna ◽

Free Dna

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Partial plasma cell differentiation as a mechanism of lost major histocompatibility complex class II expression in diffuse large B-cell lymphoma

Blood ◽

10.1182/blood-2011-07-363820 ◽

2012 ◽

Vol 119 (6) ◽

pp. 1459-1467 ◽

Cited By ~ 27

Author(s):

Sarah T. Wilkinson ◽

Kristie A. Vanpatten ◽

Diane R. Fernandez ◽

Patrick Brunhoeber ◽

Karl E. Garsha ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

B Cell ◽

Plasma Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complex Class ◽

Mhc Ii ◽

Histocompatibility Complex ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Loss of major histocompatibility complex class II (MHC II) expression is associated with poor patient outcome in diffuse large B-cell lymphoma (DLBCL). As MHC II molecules are lost with plasmacytic differentiation in normal cells, we asked whether MHC II loss in DLBCL is associated with an altered differentiation state. We used gene expression profiling, quantum dots, and immunohistochemistry to study the relationship between MHC II and plasma cell markers in DLBCL and plasmablastic lymphoma (PBL). Results demonstrate that MHC II(−) DLBCL immunophenotypically overlap with PBL and demonstrate an inverse correlation between MHC II and plasma cell markers MUM1, PRDM1/Blimp1, and XBP1s. In addition, MHC II expression is significantly higher in germinal center-DLBCL than activated B cell-DLBCL. A minor subset of cases with an unusual pattern of mislocalized punctate MHC II staining and intermediate levels of mRNA is also described. Finally, we show that PBL is negative for MHC II. The results imply a spectrum of MHC II expression that is more frequently diminished in tumors derived from B cells at the later stages of differentiation (with complete loss in PBL). Our observations provide a possible unifying concept that may contribute to the poor outcome reported in all MHC II(−) B-cell tumors.

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Biclonal IgD and IgM Plasma Cell Myeloma: A Report of Two Cases and a Literature Review

Case Reports in Hematology ◽

10.1155/2013/293150 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Zhongchuan W. Chen ◽

Ioanna Kotsikogianni ◽

Jay S. Raval ◽

Christine G. Roth ◽

Marian A. Rollins-Raval

Keyword(s):

Bone Marrow ◽

Plasma Cell ◽

Plasma Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Protein Electrophoresis ◽

Plasma Cell Myeloma ◽

Clinical Behavior ◽

Therapeutic Implications ◽

Immunohistochemical Studies

Biclonal plasma cell myelomas producing two different isotypes of immunoglobulins are extremely rare entities; to date, the combination of IgD and IgM secretion by a biclonal plasma cell myeloma has not been reported. Bone marrow biopsy immunohistochemical studies in two cases revealed neoplastic plasma cells coexpressing IgD and IgM, but serum protein electrophoresis identified only the IgM monoclonal paraprotein in both cases. Biclonal plasma cell myelomas, while currently not well characterized in terms of their clinical behavior, should be distinguished from B-cell lymphoma with plasmacytic differentiation, given the different therapeutic implications. Both cases reported herein demonstrated chemotherapy-resistant clinical courses.

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