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Article ; Online: The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa.

Vest, Stine Dahl / Eriksen, Patrick Rene Gerhard / de Groot, Fleur A / de Groen, Ruben A L / Kleij, Anne H R / Kirkegaard, Marina Knudsen / Kamper, Peter / Rasmussen, Peter Kristian / von Buchwald, Christian / de Nully Brown, Peter / Kiilgaard, Jens Folke / Vermaat, Joost S P / Heegaard, Steffen

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell ... ...

Abstract	To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with
MeSH term(s)	Humans ; Retrospective Studies ; DNA Copy Number Variations ; Genetic Profile ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Adaptor Proteins, Signal Transducing/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing
Language	English
Publishing date	2024-03-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063094
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Article ; Online: Shoulder movement complexity in the aging shoulder: A cross-sectional analysis and reliability assessment.

Overbeek, Celeste L / Geurkink, Timon H / de Groot, Fleur A / Klop, Ilse / Nagels, Jochem / Nelissen, Rob G H H / de Groot, Jurriaan H

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2020 Volume 39, Issue 10, Page(s) 2217–2225

Abstract: Healthy individuals perform a task such as hitting the head of a nail with an infinite coordination spectrum. This motor redundancy is healthy and allows for learning through exploration and uniform load distribution across muscles. Assessing movement ... ...

Abstract	Healthy individuals perform a task such as hitting the head of a nail with an infinite coordination spectrum. This motor redundancy is healthy and allows for learning through exploration and uniform load distribution across muscles. Assessing movement complexity within repetitive movement trajectories may provide insight into the available motor redundancy during aging. We quantified complexity of repetitive arm elevation trajectories in the aging shoulder and assessed test-retest reliability of this quantification. In a cross-sectional study using 3D-electromagnetic tracking, 120 asymptomatic subjects, aged between 18 and 70 years performed repetitive abduction and forward/anteflexion movements. Movement complexity was calculated using the Approximate Entropy (ApEn-value): [0,2], where lower values indicate reduced complexity. Thirty-three participants performed the protocol twice, to determine reliability (intraclass correlation coefficient [ICC]). The association between age and ApEn was corrected for task characteristics (e.g., sample length) with multiple linear regression analysis. Reproducibility was determined using scatter plots and ICC's. Higher age was associated with lower ApEn-values during abduction (unstandardized estimate: -0.003/year; 95% confidence interval: [-0.005; -0.002]; p < .001). ICC's revealed poor to good reliability depending on differences in sample length between repeated measurements. The results may imply more stereotype movement during abduction in the ageing shoulder, making this movement prone to the development of shoulder complaints. Future studies may investigate the pathophysiology and clinical course of shoulder complaints by assessment of movement complexity. To this end, the ApEn-value calculated over repetitive movement trajectories may be used, although biasing factors such as sample length should be taken into account.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aging ; Biomechanical Phenomena/physiology ; Cross-Sectional Studies ; Humans ; Middle Aged ; Movement ; Range of Motion, Articular/physiology ; Reproducibility of Results ; Shoulder ; Young Adult
Language	English
Publishing date	2020-12-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.24932
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Article ; Online: Real-world routine diagnostic molecular analysis for TP53 mutational status is recommended over p53 immunohistochemistry in B-cell lymphomas.

de Haan, Lorraine M / de Groen, Ruben A L / de Groot, Fleur A / Noordenbos, Troy / van Wezel, Tom / van Eijk, Ronald / Ruano, Dina / Diepstra, Arjan / Koens, Lianne / Nicolae-Cristea, Alina / Hartog, Wietske C E den / Terpstra, Valeska / Ahsmann, Els / Dekker, Tim J A / Sijs-Szabo, Aniko / Veelken, Hendrik / Cleven, Arjen H G / Jansen, Patty M / Vermaat, Joost S P

Virchows Archiv : an international journal of pathology

2023

Abstract: Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as ...

Abstract	Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice. For each case, p53 IHC was assigned to one of three categories: wild type (staining 1-50% of tumor cells with variable nuclear staining), abnormal complete absence or abnormal overexpression (strong and diffuse staining > 50% of tumor cells). Pathogenic variants of TP53 were identified with a targeted next generation sequencing (tNGS) panel. Wild type p53 expression was observed in 267 cases (75.4%), complete absence in twenty cases (5.7%) and the overexpression pattern in 67 cases (18.9%). tNGS identified a pathogenic TP53 mutation in 102 patients (29%). The overall accuracy of p53 IHC was 84.5% (95% CI 80.3-88.1), with a robust specificity of 92.1% (95% CI 88.0- 95.1), but a low sensitivity of 65.7% (95% CI 55.7-74.8). These results suggest that the performance of p53 IHC is insufficient as a surrogate marker for TP53 mutations in our real-world routine diagnostic workup of MBCL patients. By using p53 immunohistochemistry alone, there is a significant risk a TP53 mutation will be missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all MBCL patients, especially for further development of risk-directed therapies based on TP53 mutation status.
Language	English
Publishing date	2023-10-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-023-03676-6
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Article ; Online: Synchronous diffuse large B-cell lymphoma and mantle cell lymphoma: support for low-threshold biopsies and genetic testing.

de Groot, Fleur A / de Haan, Lorraine M / de Groen, Ruben A L / Heijmen, Linda / van Wezel, Tom / van Eijk, Ronald / Bohmer, Lara / Bot, Freek / Ten Berge, Rosita L / Diepstra, Arjan / Veelken, Hendrik / Cleven, Arjen H G / Jansen, Patty M / Vermaat, Joost S P

Leukemia & lymphoma

2021 Volume 63, Issue 5, Page(s) 1251–1255

MeSH term(s)	Adult ; Biopsy ; Genetic Testing ; Humans ; Lymphoma, Follicular/pathology ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Mantle-Cell/diagnosis ; Lymphoma, Mantle-Cell/genetics ; Lymphoma, Mantle-Cell/pathology
Language	English
Publishing date	2021-12-21
Publishing country	United States
Document type	Letter
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2021.2015589
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Article: Biological and Clinical Implications of Gene-Expression Profiling in Diffuse Large B-Cell Lymphoma: A Proposal for a Targeted BLYM-777 Consortium Panel as Part of a Multilayered Analytical Approach.

de Groot, Fleur A / de Groen, Ruben A L / van den Berg, Anke / Jansen, Patty M / Lam, King H / Mutsaers, Pim G N J / van Noesel, Carel J M / Chamuleau, Martine E D / Stevens, Wendy B C / Plaça, Jessica R / Mous, Rogier / Kersten, Marie José / van der Poel, Marjolein M W / Tousseyn, Thomas / Woei-A-Jin, F J Sherida H / Diepstra, Arjan / Nijland, Marcel / Vermaat, Joost S P

Cancers

2022 Volume 14, Issue 8

Abstract: Gene-expression profiling (GEP) is used to study the molecular biology of lymphomas. Here, advancing insights from GEP studies in diffuse large B-cell lymphoma (DLBCL) lymphomagenesis are discussed. GEP studies elucidated subtypes based on cell-of-origin ...

Abstract	Gene-expression profiling (GEP) is used to study the molecular biology of lymphomas. Here, advancing insights from GEP studies in diffuse large B-cell lymphoma (DLBCL) lymphomagenesis are discussed. GEP studies elucidated subtypes based on cell-of-origin principles and profoundly changed the biological understanding of DLBCL with clinical relevance. Studies integrating GEP and next-generation DNA sequencing defined different molecular subtypes of DLBCL entities originating at specific anatomical localizations. With the emergence of high-throughput technologies, the tumor microenvironment (TME) has been recognized as a critical component in DLBCL pathogenesis. TME studies have characterized so-called "lymphoma microenvironments" and "ecotypes". Despite gained insights, unexplained chemo-refractoriness in DLBCL remains. To further elucidate the complex biology of DLBCL, we propose a novel targeted GEP consortium panel, called BLYM-777. This knowledge-based biology-driven panel includes probes for 777 genes, covering many aspects regarding B-cell lymphomagenesis (f.e., MYC signature, TME, immune surveillance and resistance to CAR T-cell therapy). Regarding lymphomagenesis, upcoming DLBCL studies need to incorporate genomic and transcriptomic approaches with proteomic methods and correlate these multi-omics data with patient characteristics of well-defined and homogeneous cohorts. This multilayered methodology potentially enhances diagnostic classification of DLBCL subtypes, prognostication, and the development of novel targeted therapeutic strategies.
Language	English
Publishing date	2022-04-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14081857
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Article ; Online: Detection of Second Primary Lymphoma in Late Diffuse Large B-cell Lymphoma Recurrences.

Berendsen, Madeleine R / Bladel, Diede A G van / Hesius, Eva / de Groot, Fleur A / Kroeze, Leonie I / Rijntjes, Jos / Luijks, Jeroen A C W / Hoevenaars, Brigiet / Halilovic, Altuna / Nooijen, Peet / Bladel, Esther van / Jonge-Peeters, Susan de / Lensen, Chantal / Pruijt, Hans / van der Spek, Ellen / Vermaat, Joost S P / Hess, Corine / Hebeda, Konnie M / Stevens, Wendy B C /

van Krieken, J Han J M / van den Brand, Michiel / Groenen, Patricia J T A / Scheijen, Blanca

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2023 Volume 36, Issue 5, Page(s) 100119

Abstract: Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) relapse and often require salvage chemotherapy followed by autologous stem cell transplantation. In most cases, the clonal relationship between the first diagnosis and ... ...

Abstract	Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) relapse and often require salvage chemotherapy followed by autologous stem cell transplantation. In most cases, the clonal relationship between the first diagnosis and subsequent relapse is not assessed, thereby potentially missing the identification of second primary lymphoma. In this study, the clonal relationship of 59 paired DLBCL diagnoses and recurrences was established by next-generation sequencing-based detection of immunoglobulin gene rearrangements. Among 50 patients with interpretable results, 43 patients (86%) developed clonally related relapsed disease. This was observed in 100% of early recurrences (<2 years), 80% of the recurrences with an interval between 2 and 5 years, and 73% of late recurrences (≥5 years). On the other hand, 7 (14%) out of 50 patients displayed different dominant clonotypes in primary DLBCL and clinical recurrences, confirming the occurrence of second primary DLBCL; 37% of DLBCL recurrences that occurred ≥4 years after diagnosis were shown to be second primary lymphomas. The clonally unrelated cases were Epstein-Barr virus positive in 43% of the cases, whereas this was only 5% in the relapsed DLBCL cases. In conclusion, next-generation sequencing-based clonality testing in late recurrences should be considered in routine diagnostics to distinguish relapse from second primary lymphoma, as this latter group of patients with DLBCL may benefit from less-intensive treatment strategies.
MeSH term(s)	Humans ; Epstein-Barr Virus Infections/pathology ; Hematopoietic Stem Cell Transplantation ; Neoplasm Recurrence, Local/pathology ; Herpesvirus 4, Human ; Transplantation, Autologous ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/drug therapy
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2023.100119
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Article ; Online: An automated reminder for perioperative glucose regulation improves protocol compliance.

Polderman, Jorinde A W / de Groot, Fleur A / Zamanbin, Alaleh / Hollmann, Markus W / Holleman, Frits / Preckel, Benedikt / Hermanides, Jeroen

Diabetes research and clinical practice

2016 Volume 116, Page(s) 80–82

Abstract: A growing proportion of patients presenting for surgery have diabetes. Unfortunately, perioperative diabetes protocol compliance is low. Using digitalization of the perioperative environment, an automated reminder in the preoperative assessment platform ... ...

Abstract	A growing proportion of patients presenting for surgery have diabetes. Unfortunately, perioperative diabetes protocol compliance is low. Using digitalization of the perioperative environment, an automated reminder in the preoperative assessment platform proved to increase compliance and we advocate its use throughout the perioperative process.
MeSH term(s)	Analysis of Variance ; Blood Glucose/analysis ; Diabetes Mellitus/drug therapy ; Guideline Adherence/standards ; Humans ; Perioperative Care/methods ; Prospective Studies ; Reminder Systems
Chemical Substances	Blood Glucose
Language	English
Publishing date	2016-06
Publishing country	Ireland
Document type	Journal Article ; Observational Study
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2016.04.010
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Article ; Online: A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma.

van Bladel, Diede A G / Stevens, Wendy B C / Kroeze, Leonie I / de Groen, Ruben A L / de Groot, Fleur A / van der Last-Kempkes, Jessica L M / Berendsen, Madeleine R / Rijntjes, Jos / Luijks, Jeroen A C W / Bonzheim, Irina / van der Spek, Ellen / Plattel, Wouter J / Pruijt, Johannes F M / de Jonge-Peeters, Susan D P W M / Velders, Gerjo A / Lensen, Chantal / van Bladel, Esther R / Federmann, Birgit / Hoevenaars, Brigiet M /

Pastorczak, Agata / van der Werff Ten Bosch, Jutte / Vermaat, Joost S P / Nooijen, Peet T G A / Hebeda, Konnie M / Fend, Falko / Diepstra, Arjan / van Krieken, J Han J M / Groenen, Patricia J T A / van den Brand, Michiel / Scheijen, Blanca

Blood advances

2023 Volume 7, Issue 19, Page(s) 5911–5924

Abstract: Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is underinvestigated. To analyze the nature of cHL recurrences, ...

Abstract	Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is underinvestigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements was performed in paired cHL diagnoses and recurrences among 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal Ig rearrangements were detected by next-generation sequencing (NGS) in 69 of 120 (58%) diagnoses and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24 of 34 patients (71%). Clonally unrelated cHL was observed in 10 of 34 patients (29%) as determined by IG-NGS clonality assessment and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of >2 years, ∼60% of patients with cHL for whom the clonal relationship could be established showed a second primary cHL. Clonal TCR gene rearrangements were identified in 14 of 125 samples (11%), and TCL-associated gene mutations were detected in 7 of 14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged >50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based Ig/TCR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.
MeSH term(s)	Humans ; Hodgkin Disease/diagnosis ; Hodgkin Disease/genetics ; Hodgkin Disease/pathology ; Retrospective Studies ; Neoplasm Recurrence, Local ; Lymphoma ; Lymphoma, T-Cell ; Immunoglobulins
Chemical Substances	Immunoglobulins
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010412
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Article ; Online: Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.

de Groen, Ruben A L / van Eijk, Ronald / Böhringer, Stefan / van Wezel, Tom / Raghoo, Richard / Ruano, Dina / Jansen, Patty M / Briaire-de Bruijn, Inge / de Groot, Fleur A / Kleiverda, Karin / Te Boome, Liane / Terpstra, Valeska / Levenga, Henriette / Nicolae, Alina / Posthuma, Eduardus F M / Focke-Snieders, Isabelle / Hardi, Lizan / den Hartog, Wietske C E / Bohmer, Lara H /

Hogendoorn, Pancras C W / van den Berg, Anke / Diepstra, Arjan / Nijland, Marcel / Lugtenburg, Pieternella J / Kersten, Marie José / Pals, Steven T / Veelken, Hendrik / Bovée, Judith V M G / Cleven, Arjen H G / Vermaat, Joost S P

Blood advances

2021 Volume 5, Issue 19, Page(s) 3760–3775

Abstract: Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O- ... ...

Abstract	Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Cell-of-origin was determined by immunohistochemistry and gene-expression profiling (GEP) using (extended)-NanoString/Lymph2Cx analysis. Mutational profiles were identified with targeted next-generation deep sequencing, including 52 B-cell lymphoma-relevant genes. O-DLBCLs, including 34 PB-DLBCLs, were predominantly classified as GCB phenotype based on immunohistochemistry (74%) and NanoString analysis (88%). Unsupervised hierarchical clustering of an extended-NanoString/Lymph2Cx revealed significantly different GEP clusters for PB-DLBCL as opposed to NO-DLBCL-GCB (P < .001). Expression levels of 23 genes of 2 different targeted GEP panels indicated a centrocyte-like phenotype for PB-DLBCL, whereas NO-DLBCL-GCB exhibited a centroblast-like constitution. PB-DLBCL had significantly more frequent mutations in four GCB-associated genes (ie, B2M, EZH2, IRF8, TNFRSF14) compared with NO-DLBCL-GCB (P = .031, P = .010, P = .047, and P = .003, respectively). PB-DLBCL, with its corresponding specific mutational profile, was significantly associated with a superior survival compared with equivalent Ann Arbor limited-stage I/II NO-DLBCL-GCB (P = .016). This study is the first to show that PB-DLBCL is characterized by a GCB phenotype, with a centrocyte-like GEP pattern and a GCB-associated mutational profile (both involved in immune surveillance) and a favorable prognosis. These novel biology-associated features provide evidence that PB-DLBCL represents a distinct extranodal DLBCL entity, and its specific mutational landscape offers potential for targeted therapies (eg, EZH2 inhibitors).
MeSH term(s)	Enhancer of Zeste Homolog 2 Protein/genetics ; Germinal Center/metabolism ; Humans ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Lymphoma, Large B-Cell, Diffuse/genetics ; Phenotype ; Receptors, Tumor Necrosis Factor, Member 14 ; Retrospective Studies
Chemical Substances	Interferon Regulatory Factors ; Receptors, Tumor Necrosis Factor, Member 14 ; TNFRSF14 protein, human ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43)
Language	English
Publishing date	2021-12-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021005215
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