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Joost Kluiver
dr.

I have a central role in all research projects focusing on the role of noncoding RNAs. My main aim is to understanding how small and long non-coding RNAs contribute to the pathogenesis of B-cell lymphoma. Ongoing studies include MYC-regulated miRNAs and lncRNAs, as well as miRNA-lncRNA interactions and the role of circular RNAs. We apply state-of-the-art methodology including AGO2-RIP, RNA-FISH and gain- and loss-of-function screens using shRNA and CRISPR-Cas technology.

Metastatic mismatch repair deficient oesophageal squamous cell carcinoma leading to diagnosis of Lynch syndrome with a complete response to nivolumab treatment
Published in: Virchows Archiv : an International Journal of Pathology
A 59-year-old woman with two colorectal adenocarcinomas in 2015 and 2022 (both with loss of MSH2 and focal presence of MSH6 protein, thus MMR-deficient profile) had a variant of c.1012G > C p.(Gly338Arg) in the MSH2 gene, classified as Variant of Uncertain Significance (VUS) in 2023. That year, she was also diagnosed with oesophageal squamous cell carcinoma (ESCC), again MMR-deficient. Although uncommon, a proportion of ESCC can be MMR-deficient. The ESCC showed complete response to nivolumab. Genetic studies of the three tumours showed the same germline variant. During follow-up, the...
Palmitoylation by ZDHHC family members regulate B-cell lymphoma growth
Published in: International Journal of Biological Macromolecules
The ZDHHC palmitoyl transferase family consists of 24 members, of which several have been linked to the development of cancer. We previously showed that inhibition of ZDHHC11 decreased growth of several B-cell lymphoma subtypes. In this study, we evaluated the effect of protein palmitoylation on the proteome in general and investigated expression and function of ZDHHC family members in a panel of Burkitt, Hodgkin and diffuse large B-cell lymphoma cell lines. Proteomic analysis of Burkitt lymphoma cells treated with the general palmitoylation inhibitor 2-bromopalmitate (2-BP) revealed 1089 differentially...
Yichen Liu, Shiyun Hu, Özlem Önder, Anagh Sahasrabuddhe, Ali Rajabi, Annika Seitz, Debora de Jong, Jasper Koerts, Lydia Visser, Agnieszka Dzikiewicz-Krawczyk, Megan S Lim, Kojo S Elenitoba-Johnson, Anke van den Berg, Lotteke J Y M Ziel-Swier, Joost Kluiver
miRNA-dependent resistance mechanisms to anti-hormonal therapies in estrogen receptor-positive breast cancer patients
Published in: Molecular therapy. Oncology
The estrogen receptor (ERα) is expressed in 70%-80% of breast cancers and is a target of endocrine therapy. However, resistance to endocrine therapy poses a significant clinical challenge. MicroRNAs (miRNAs) have emerged as critical players in oncogenesis and as modulators of therapy response. This review provides an overview of miRNAs that modulate anti-hormonal drug responses. We identified 56 miRNAs associated with resistance to endocrine therapy. These miRNAs had a total of 40 proven target genes that were grouped based on their function under currently known resistance mechanisms, including...
Molecular profiling of cell-free DNA from classic Hodgkin lymphoma patients identifies potential prognostic clusters and corresponds with disease dynamics
Published in: Annals of Hematology
Cell-free DNA (cfDNA) analysis has advantages over tissue analysis for molecular profiling of classic Hodgkin lymphoma (cHL) at diagnosis and offers additional opportunities for sensitive non-invasive disease tracking during treatment. The aim of this study is to correlate cfDNA based molecular profiling with disease characteristics including serum Thymus and Activation Regulated Chemokine (TARC) levels and FDG-PET imaging, which are established markers of disease assessment. cfDNA isolated from plasma samples of 42 cHL patients was analyzed using low coverage whole genome and targeted next-generation sequencing. Patients were clustered in...
An Unexpected Finding of a PTPN11 Germline Mutation in a Patient With a Melanocytic Lesion With a Somatic MAP2K1 Mutation. Coincidence or Not?
Published in: Journal of Cutaneous Pathology
Melanocytic tumors are a diverse group of lesions and are traditionally classified based on a combination of clinical presentation as well as histological examination. More recently, molecular diagnostics has become an increasingly important part of differentiating different melanocytic lesions in the current WHO standards. This molecular testing, however, can result in unexpected findings. In this report, we describe that molecular testing of a clinical atypical melanocytic lesion showed a mutation in the MAP2K1 gene as well as an unexpected germline mutation in PTPN11, indicative of Noonan syndrome. Based...
Sven van der Woude, J S Klein Wassink-Ruiter, Joost Kluiver, Marthe de Jonge, Gilles F H Diercks