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Article ; Online: Gene Expression Profiling Suggests that Complement Activation Is Important for Blister Formation in Bullous Pemphigoid.

Lamberts, Aniek / Kotnik, Nika / Meijer, Joost M / van Kempen, Leon C / Diercks, Gilles F H / Horváth, Barbara

The Journal of investigative dermatology

2023 Volume 143, Issue 8, Page(s) 1591–1594.e2

MeSH term(s)	Humans ; Pemphigoid, Bullous/genetics ; Pemphigoid, Bullous/metabolism ; Blister/genetics ; Blister/metabolism ; Skin Diseases ; Complement Activation/genetics ; Gene Expression Profiling
Language	English
Publishing date	2023-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.01.029
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Article ; Online: A novel PPP2R2A::PRKD1 fusion in a cribriform adenocarcinoma of salivary gland.

de Jager, Vincent D / de Visscher, Sebastiaan A H J / Schuuring, Ed / Doff, Jan J / van Kempen, Léon C

Genes, chromosomes & cancer

2023 Volume 62, Issue 5, Page(s) 297–300

Abstract: Cribriform adenocarcinoma of salivary gland (CASG) is a rare, salivary gland tumor. In this report, we describe a case of CASG harboring a novel PPP2R2A::PRKD1 fusion. A 58-year-old female presented with an intraoral mass adjacent to the lower left third ...

Abstract	Cribriform adenocarcinoma of salivary gland (CASG) is a rare, salivary gland tumor. In this report, we describe a case of CASG harboring a novel PPP2R2A::PRKD1 fusion. A 58-year-old female presented with an intraoral mass adjacent to the lower left third molar region. Morphological features at histological examination, immunohistochemical staining (p63+, p40-), and tumor location were indicative of CASG. However, due to the potential focal presence of a biphasic component within the tumor, RNA sequencing was performed to confirm the diagnosis. The subsequently found novel PPP2R2A::PRKD1 fusion adds to the rapidly evolving molecular landscape of salivary gland tumors. Additionally, we report that CASG may show some entrapment of pre-existent salivary gland ducts, which may be misinterpreted as tumor cells with myoepithelial differentiation.
MeSH term(s)	Female ; Humans ; Middle Aged ; Adenocarcinoma/pathology ; Salivary Glands ; Transcription Factors ; Salivary Gland Neoplasms/pathology ; Biomarkers, Tumor/genetics ; Protein Phosphatase 2/genetics
Chemical Substances	Transcription Factors ; Biomarkers, Tumor ; PPP2R2A protein, human ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2023-02-03
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23122
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Zs.A 2966: Show issues

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Article: Detection of

Koopman, Bart / Kuijpers, Chantal C H J / Groen, Harry J M / Timens, Wim / Schuuring, Ed / Willems, Stefan M / van Kempen, Léon C

Diagnostics (Basel, Switzerland)

2022 Volume 12, Issue 3

Abstract: Gene fusions ... ...

Abstract	Gene fusions involving
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12030668
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Article ; Online: Prevalence of KRAS p.(G12C) in stage IV NSCLC patients in the Netherlands; a nation-wide retrospective cohort study.

Garcia, Betzabel N Cajiao / van Kempen, Léon C / Kuijpers, Chantal C H J / Schuuring, Ed / Willems, Stefan M / van der Wekken, Anthonie J

Lung cancer (Amsterdam, Netherlands)

2022 Volume 167, Page(s) 1–7

Abstract: Objectives: The recent accelerated FDA approval of sotorasib, a highly selective KRAS G12C inhibitor, offers new opportunities for the treatment of KRAS p.(G12C)-mutated non-squamous non-small cell lung cancer (NSCLC). The objective of the current study ...

Abstract	Objectives: The recent accelerated FDA approval of sotorasib, a highly selective KRAS G12C inhibitor, offers new opportunities for the treatment of KRAS p.(G12C)-mutated non-squamous non-small cell lung cancer (NSCLC). The objective of the current study was to the determine the prevalence of KRAS mutations in stage IV non-squamous NSCLC in The Netherlands to reveal the potential impact of upcoming KRAS targeted therapy. Materials and methods: All patients diagnosed with stage IV non-squamous NSCLC in 2013, 2015 and 2017 in the Netherlands were selected by linking the nation-wide Netherlands Cancer Registry (NCR) and the Dutch Pathology Registry (PALGA). Demographic and pathological variables were retrieved from the pathology reports including sex, age, KRAS mutation status, molecular test method used, and the mutation status of other genes. Results: Prevalence for any KRAS mutations in codon 12/13/61/146 was 39.1%. KRAS p.(G12C) was detected in 15.5% of all non-squamous NSCLC cases representing 39.6% of all KRAS-mutant cases. National testing rate for KRAS mutations increased from 70% in 2013 to 82% in 2017. Testing techniques changed significantly over time with next generation sequencing as the main used method in 2017 (71.6%) but did not affect prevalence of KRAS mutations over time. When KRAS was tested as part of a larger panel, the KRAS p.(G12C) mutation was frequently reported with a concurrent mutation in TP53 (47.7%) or STK11 (10.3%). Conclusion: The high prevalence for KRAS p.(G12C) offers a promising new specific treatment option for 15% of all stage IV non-squamous NSCLC patients.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/epidemiology ; Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/epidemiology ; Lung Neoplasms/genetics ; Netherlands/epidemiology ; Prevalence ; Proto-Oncogene Proteins p21(ras)/genetics ; Retrospective Studies
Chemical Substances	KRAS protein, human ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2022-03-24
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2022.03.015
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Increased Interferon Signalling in Vaginal Tissue of Patients With Primary Sjögren Syndrome.

Visser, Annie / van Nimwegen, Jolien F / Wilbrink, Rick / Liefers, Silvia C / van der Tuuk, Karin / Mourits, Marian J E / Diercks, Gilles F H / Bart, Joost / van der Vegt, Bert / van Kempen, Léon C / Bootsma, Hendrika / Kroese, Frans G M / Verstappen, Gwenny M

The Journal of rheumatology

2024

Abstract: Objective: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. ... ...

Abstract	Objective: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in the vaginal tissue of patients with pSS. Methods: Vaginal biopsies of 8 premenopausal patients with pSS experiencing vaginal dryness and 7 age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using NanoString technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells [pDCs]). Results: The most enriched pathway in vaginal biopsies from patients with pSS compared to non-pSS controls was the interferon (IFN) signaling pathway ( Conclusion: Upregulation of IFN signaling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology (ie, vaginal dryness).
Language	English
Publishing date	2024-05-15
Publishing country	Canada
Document type	Journal Article
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.2023-1068
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Zs.A 1168: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 135: Show issues

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Article ; Online: Diagnostic yield of NanoString nCounter FusionPlex profiling in soft tissue tumors.

Song, Wangzhao / Platteel, Inge / Suurmeijer, Albert J H / van Kempen, Léon C

Genes, chromosomes & cancer

2020 Volume 59, Issue 5, Page(s) 318–324

Abstract: Diagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor-defining gene translocations, which may provide an important ancillary tool ...

Abstract	Diagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor-defining gene translocations, which may provide an important ancillary tool for tumor diagnosis. The NanoString nCounter platform enables multiplex detection of pre-defined gene fusion transcripts in formalin-fixed and paraffin-embedded tissue. A cohort of 104 soft tissue tumors representing 20 different histological types was analyzed for the expression of 174 unique gene fusion transcripts. A tumor-defining gene fusion transcript was detected in 60 cases (58%). Sensitivity and specificity of the NanoString assay calculated against the result of an alternative molecular method were 85% and 100%, respectively. Highest diagnostic coverage was obtained for Ewing sarcoma, synovial sarcoma, myxoid liposarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor. For these tumor types, the NanoString assay is a rapid, cost-effective, sensitive, and specific ancillary screening tool for molecular diagnosis. For other sarcomas, additional molecular testing may be required when a translocation transcript is not identified with the current 174 gene fusion panel.
MeSH term(s)	Biomarkers, Tumor/genetics ; Cohort Studies ; Gene Rearrangement ; Humans ; Oncogene Proteins, Fusion/genetics ; Paraffin Embedding/methods ; Soft Tissue Neoplasms/classification ; Soft Tissue Neoplasms/diagnosis ; Soft Tissue Neoplasms/genetics ; Translocation, Genetic
Chemical Substances	Biomarkers, Tumor ; Oncogene Proteins, Fusion
Language	English
Publishing date	2020-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.22834
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Article ; Online ; Conference proceedings: 5th Canadian Melanoma Conference: research frontiers.

van Kempen, Léon C

Expert review of anticancer therapy

2011 Volume 11, Issue 6, Page(s) 845–848

Abstract: The prospects for the treatment of metastatic melanoma are improving. Whereas previous scientific meetings dedicated to the treatment of metastatic melanoma patients were overshadowed by our inability to improve overall survival or lengthen the time to ... ...

Abstract	The prospects for the treatment of metastatic melanoma are improving. Whereas previous scientific meetings dedicated to the treatment of metastatic melanoma patients were overshadowed by our inability to improve overall survival or lengthen the time to progression, the results presented at the most recent meetings are hopeful. The 5th Canadian Melanoma Conference held on 24-27 February in Banff (AB, Canada) was nothing short of optimistic. This year's meeting was divided into three themes: basic science and pathology, dermatology and surgery, and immunology and systemic treatment. In addition, dermoscopy case studies were presented, and Hoffmann la Roche sponsored a symposium on the evaluation of treatment for advanced melanoma. It underscored the importance of early detection and patient stratification, based upon the molecular profile of the tumor, in order to optimize the response to targeted therapy.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Canada ; Disease Progression ; Drug Delivery Systems ; Early Detection of Cancer ; Humans ; Melanoma/pathology ; Melanoma/therapy ; Neoplasm Metastasis ; Skin Neoplasms/pathology ; Skin Neoplasms/therapy ; Survival
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2011-06
Publishing country	England
Document type	Congresses
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1586/era.11.62
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Zs.A 5907: Show issues

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Article ; Online: Angiosarcomatous transdifferentiation of metastatic melanoma.

Kilsdonk, Melvin J / Romeijn, Tonnis R / Kelder, Wendy / van Kempen, Léon C / Diercks, Gilles F

Journal of cutaneous pathology

2020 Volume 47, Issue 12, Page(s) 1211–1214

Abstract: Melanoma is known to show considerable variation in its histopathological presentation. In exceptional cases, heterologous or divergent differentiation (metaplastic melanoma) can be observed. We report a case of a 69-year-old man who was diagnosed with ... ...

Abstract	Melanoma is known to show considerable variation in its histopathological presentation. In exceptional cases, heterologous or divergent differentiation (metaplastic melanoma) can be observed. We report a case of a 69-year-old man who was diagnosed with nodular melanoma on the right upper leg. One year later, the patient presented with an inguinal lymph node metastasis and a lymph node dissection was carried out. In two out of five positive lymph nodes, an angiosarcomatous component was found next to a conventional melanoma component. Shortly after, the patient developed two in-transit metastases in which again an angiosarcomatous component was seen. The vascular component stained positive for ERG and CD31 and negative for melanocytic markers (Mart-1, S100, SOX-10), while the conventional melanoma had an opposite staining pattern. Molecular analysis on both components showed an identical mutation in the NRAS gene, which in our opinion proves the divergent differentiation. To the best of our knowledge, this is the first case report describing angiosarcomatous transdifferentiation of melanoma.
MeSH term(s)	Aged ; Cell Transdifferentiation/genetics ; GTP Phosphohydrolases/genetics ; Hemangiosarcoma/blood supply ; Hemangiosarcoma/drug therapy ; Hemangiosarcoma/metabolism ; Hemangiosarcoma/pathology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunohistochemistry ; Inguinal Canal/pathology ; Lymph Node Excision/methods ; Lymphatic Metastasis/diagnosis ; Male ; Melanoma/secondary ; Membrane Proteins/genetics ; Mutation ; Nivolumab/therapeutic use ; Palliative Care ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Skin Neoplasms/secondary ; Transcriptional Regulator ERG/metabolism ; Treatment Outcome ; Melanoma, Cutaneous Malignant
Chemical Substances	ERG protein, human ; Immune Checkpoint Inhibitors ; Membrane Proteins ; PECAM1 protein, human ; Platelet Endothelial Cell Adhesion Molecule-1 ; Transcriptional Regulator ERG ; Nivolumab (31YO63LBSN) ; GTP Phosphohydrolases (EC 3.6.1.-) ; NRAS protein, human (EC 3.6.1.-)
Language	English
Publishing date	2020-09-28
Publishing country	United States
Document type	Case Reports
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.13857
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Zs.A 1043: Show issues

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Article ; Online: Analysis of the Tumor Microenvironment Transcriptome via NanoString mRNA and miRNA Expression Profiling.

M'Boutchou, Marie-Noël / van Kempen, Léon C

Methods in molecular biology (Clifton, N.J.)

2016 Volume 1458, Page(s) 291–310

Abstract: Unlabelled: Gene expression analysis in the tumor microenvironment using archived clinical samples is challenging because of formalin fixation, RNA degradation, and limiting sample volume. NanoString gene expression profiling is a RNA-DNA hybrid capture ...

Abstract	Unlabelled: Gene expression analysis in the tumor microenvironment using archived clinical samples is challenging because of formalin fixation, RNA degradation, and limiting sample volume. NanoString gene expression profiling is a RNA-DNA hybrid capture technology that does not require PCR and can accurately quantify the expression of to 800 transcripts in a single reaction. The technology requires 50-100 ng of RNA, which can be degraded ( Editor: is this correct?) to a 200 bp fragment size. In contrast to amplification technologies, nanoString counts the actual numbers of transcripts that are captured with transcript-specific and fluorescently-barcoded probes. This chapter describes protocols for RNA extraction, quantification, mRNA and miRNA profiling and data analysis.
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-3801-8_21
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Article ; Online: CD4+ T cells in classical Hodgkin lymphoma express exhaustion associated transcription factors TOX and TOX2: Characterizing CD4+ T cells in Hodgkin lymphoma.

Veldman, Johanna / Rodrigues Plaça, Jessica / Chong, Lauren / Terpstra, Miente Martijn / Mastik, Mirjam / van Kempen, Léon C / Kok, Klaas / Aoki, Tomohiro / Steidl, Christian / van den Berg, Anke / Visser, Lydia / Diepstra, Arjan

Oncoimmunology

2022 Volume 11, Issue 1, Page(s) 2033433

Abstract: In classical Hodgkin lymphoma (cHL), the highly abundant CD4+ T cells in the vicinity of tumor cells are considered essential for tumor cell survival, but are ill-defined. Although they are activated, they consistently lack expression of activation ... ...

Abstract	In classical Hodgkin lymphoma (cHL), the highly abundant CD4+ T cells in the vicinity of tumor cells are considered essential for tumor cell survival, but are ill-defined. Although they are activated, they consistently lack expression of activation marker CD26. In this study, we compared sorted CD4+CD26- and CD4+CD26+ T cells from cHL lymph node cell suspensions by RNA sequencing and T cell receptor variable gene segment usage analysis. This revealed that although CD4+CD26- T cells are antigen experienced, they have not clonally expanded. This may well be explained by the expression of exhaustion associated transcription factors
MeSH term(s)	CD4-Positive T-Lymphocytes ; Dipeptidyl Peptidase 4/immunology ; HMGB Proteins/biosynthesis ; HMGB Proteins/immunology ; High Mobility Group Proteins/biosynthesis ; High Mobility Group Proteins/immunology ; Hodgkin Disease/genetics ; Hodgkin Disease/immunology ; Hodgkin Disease/metabolism ; Humans ; Lymph Nodes/pathology ; Transcription Factors/genetics
Chemical Substances	HMGB Proteins ; High Mobility Group Proteins ; TOX protein, human ; Tox2 protein, human ; Transcription Factors ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
Language	English
Publishing date	2022-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.1080/2162402X.2022.2033433
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