Our research focuses on improving molecular diagnostic methods, driving innovation in this field, and facilitating their implementation in clinical practice. We develop and evaluate innovative molecular assays, targeted sequencing panels, bioinformatic pipelines, and diagnostic workflows to increase the accuracy, efficiency, and clinical utility of genomic testing. In addition, we investigate novel applications of liquid biopsies and other minimally invasive approaches for molecular diagnostics.
A major research theme is the molecular diagnostics of tumors, with a special focus on hereditary colorectal cancer and polyposis. We study both patients with a familial predisposition and younger patients without an obvious family history. Using targeted Next Generation Sequencing, exome sequencing, transcriptome analyses, and tumor-first approaches, we identify known and novel cancer predisposition genes and characterize tumor-specific genomic profiles.
Our work particularly addresses hereditary cancer genes such as TP53, mismatch repair (MMR) genes, APC, POLE, POLD1, MUTYH, and NTHL1. Current projects focus on mutation signatures, mosaicism—including APC mosaicism—transcript variation, and genotype–phenotype correlations. Through these studies, we aim to improve genetic diagnostics, risk assessment, and personalized patient management for individuals and families affected by hereditary cancer syndromes.
Research aims:
- Innovating molecular diagnostic technologies
- Advancing liquid biopsy applications
Selected publications
Terlouw, D. et al. Prevalence and consequences of APC mosaicism in patients with colorectal adenomas. Gastroenterology 2026, doi:10.1053/j.gastro.2025.10.028.
Witjes V.M. et al. Evaluation of homologous recombination testing in ovarian carcinoma. Virchows Arch. 2026 Apr;488(4):777-788.
van Linder, B.M.H. et al. Improving the diagnosis of leptomeningeal metastases by molecular profiling of cell-free DNA from cerebrospinal fluid. Eur. J. Cancer 229, 115783 (2025).
Burghout K.S.T. et al. Molecular Analysis in Salivary Gland Tumors: Exploring the Diagnostic and Clinical Impact of Comprehensive Next Generation RNA Sequencing ("SalvGlandDx v2"). Head Neck Pathol. 2025 Dec 22;20(1):2.
Burghout K.S.T. et al. Recurrent MDM2 Amplification in the Spectrum of HMGA2-Altered Pleomorphic Adenoma, Atypical Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma. Head Neck Pathol. 2025 May 8;19(1):56.
Borm F.J. et al. Liquid biopsy in BALF is now suitable for clinical practice in patients with suspected NSCLC. Lung Cancer. 2025 Nov;209:108771.
Kemps, P.G. et al. Recurrent ETV3::NCOA2 fusions and MAPK pathway mutations in indeterminate dendritic cell histiocytosis. Blood Adv. 9, 439–444 (2025).
van der Meulen M.. An Unexpected Case of Somatic Mosaicism of the Dutch p16-Leiden Founder Variant in the CDKN2A Gene. Case Rep Genet. 2025 Aug 28;2025:6261903
Kemps, P.G. et al. Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue. Blood 144, 2439–2455 (2024).
Schubert, S.A. et al. Germline variant affecting p53β isoforms predisposes to familial cancer. Nat. Commun. 15, 8208 (2024).
Terlouw, D. et al. APC mosaicism, not always isolated: two first-degree relatives with apparently distinct APC mosaicism. Gut 72, 2186–2187 (2023).
Helderman, N.C. et al. Molecular profile of MSH6-associated colorectal carcinomas shows distinct features from other Lynch syndrome-associated colorectal carcinomas. Gastroenterology 165, 271–274.e2 (2023).
Kemps, P.G. et al. Clinicogenomic associations in childhood Langerhans cell histiocytosis: an international cohort study. Blood Adv. 7, 664–679 (2023).
Hondelink, L.M. et al. The sensitivity of pan-TRK immunohistochemistry in solid tumours: a meta-analysis. Eur. J. Cancer 173, 229–237 (2022).
Dinjens, W.N.M., Ligtenberg, M.J.L., van Wezel, T., Schuuring, E. & Dubbink, H.J. The leading role of pathology in assessing the somatic molecular alterations of cancer: Position Paper of the European Society of Pathology. Virchows Arch. 478, 379–380 (2021).
Hondelink, L.M. et al. Real-World Approach for Molecular Analysis of Acquired EGFR Tyrosine Kinase Inhibitor Resistance Mechanisms in NSCLC. JTO Clin. Res. Rep. 2, 100252 (2021).
Hondelink, L., Cohen, D., von der Thusen, J., Dubbink, E.J., van Wezel, T. & Monkhorst, K. Best practice recommendations for molecular analysis of acquired EGFR TKI resistance mechanisms. J. Thorac. Oncol. 16, S771 (2021).
Elsayed, F.A. et al. Monoallelic NTHL1 loss-of-function variants and risk of polyposis and colorectal cancer. Gastroenterology 159, 2241–2243.e6 (2020).
Terlouw, D., Suerink, M., Boot, A., van Wezel, T., Nielsen, M. & Morreau, H. Recurrent APC Splice Variant c.835-8A>G in Patients With Unexplained Colorectal Polyposis Fulfilling the Colibactin Mutational Signature. Gastroenterology 159, 1612–1614.e5 (2020).
Grolleman, J.E. et al. Mutational signature analysis reveals NTHL1 deficiency to cause a multi-tumor phenotype. Cancer Cell 35, 256–266.e5 (2019).
de Jonge, M.M. et al. Validation and Implementation of BRCA1/2 Variant Screening in Ovarian Tumor Tissue. J. Mol. Diagn. 20, 600–611 (2018).
