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Personal profile
Research interests
MYCN pathway and genomic aberrations in neuroblastoma Neuroblastoma is an embryonic tumor derived from the peripheral nervous system. Neuroblastoma is highly heterogeneous in histology, molecular biology and outcome. Genomic aberrations that exist of whole chromosome gains and losses are found in favorable tumors. MYCN (chromosome 2p) is amplified in 20% of neuroblastoma tumors and these tumors follow a particular aggressive course. Other frequent events involve chromosome 1p, 11q and 17q. Interestingly, loss of chromosome 1p and gain of 17q frequently occur in tumors with MYCN amplification.
Previously, we silenced MYCN in a MYCN-amplified cell line, measured expression changes (Affymetrix Array profiling) and integrated these data with neuroblastoma tumors . This resulted in a mycn-157 signature that predicts poor clinical outcome of neuroblastoma patients with and without MYCN amplification. Tissue array analysis of MYCN protein showed that the latter group has increased MYCN protein expression in tumor cells.
Currently we are investigating the involvement of other chromosomal aberrations that occur in neuroblastoma tumors. Using complete genomic sequencing data we can exactly determine the break point regions and identify mutated genes. Silencing (shRNA) and induction of candidate genes in neuroblastoma cell lines will identify genes involved in neuroblastoma development and MYCN stability.
Previously, we silenced MYCN in a MYCN-amplified cell line, measured expression changes (Affymetrix Array profiling) and integrated these data with neuroblastoma tumors . This resulted in a mycn-157 signature that predicts poor clinical outcome of neuroblastoma patients with and without MYCN amplification. Tissue array analysis of MYCN protein showed that the latter group has increased MYCN protein expression in tumor cells.
Currently we are investigating the involvement of other chromosomal aberrations that occur in neuroblastoma tumors. Using complete genomic sequencing data we can exactly determine the break point regions and identify mutated genes. Silencing (shRNA) and induction of candidate genes in neuroblastoma cell lines will identify genes involved in neuroblastoma development and MYCN stability.
specialisation
Molecular Biology/Oncology
Collaborations and top research areas from the last five years
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Projects
- 1 Active
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Versteeg R.: Regulatory networks in cancer
Commandeur, M., Eleveld, T., Hakkert, A., Lecca, M., Nowakowska, N., Versteeg, R., Koster, J., Valentijn, L., Hamdi, M., van Nes, J., Westerhout, E. M., Molenaar, P. & Dolman, E.
1/01/2006 → …
Project: Research
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Erratum: Mesenchymal-Type Neuroblastoma Cells Escape ALK Inhibitors (Cancer Res (2022) 82 (484–496) DOI: 10.1158/0008-5472.CAN-21-1621)
Westerhout, E. M., Hamdi, M., Stroeken, P., Nowakowska, N. E., Lakeman, A., van Arkel, J., Hasselt, N. E., Blejlevens, B., Akogul, N., Haneveld, F., Chan, A., van Sluis, P., Zwijnenburg, D., Volckmann, R., van Noesel, C. J. M., Adameyko, I., van Gronigen, T., Koster, J., Valentijn, L. J., van Nes, J., & 1 others , 15 Jul 2022, In: Cancer research. 82, 14, p. 2657 1 p.Research output: Contribution to journal › Comment/Letter to the editor › Academic
Open Access -
Mesenchymal-Type Neuroblastoma Cells Escape ALK Inhibitors
Westerhout, E. M., Hamdi, M., Stroeken, P., Nowakowska, N. E., Lakeman, A., van Arkel, J., Hasselt, N. E., Bleijlevens, B., Akogul, N., Haneveld, F., Chan, A., van Sluis, P., Zwijnenburg, D., Volckmann, R., van Noesel, C. J. M., Adameyko, I., van Groningen, T., Koster, J., Valentijn, L. J., van Nes, J., & 1 others , 1 Feb 2022, In: Cancer research. 82, 3, p. 484-496 13 p.Research output: Contribution to journal › Article › Academic › peer-review
9 Citations (Scopus) -
Urinary 3-Methoxytyramine Is a Biomarker for MYC Activity in Patients With Neuroblastoma
Verly, I. R. N., Matser, Y. A. H., Leen, R., Meinsma, R., Fiocco, M., Koster, J., Volckmann, R., Savci-Heijink, D., Cangemi, G., Barco, S., Valentijn, L. J., Tytgat, G. A. M. & van Kuilenburg, A. B. P., 2022, In: JCO Precision Oncology. 6, e2000447.Research output: Contribution to journal › Article › Academic › peer-review
Open Access3 Citations (Scopus) -
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma
van Groningen, T., Akogul, N., Westerhout, E. M., Chan, A., Hasselt, N. E., Zwijnenburg, D. A., Broekmans, M., Stroeken, P., Haneveld, F., Hooijer, G. K. J., Savci-Heijink, C. D., Lakeman, A., Volckmann, R., van Sluis, P., Valentijn, L. J., Koster, J., Versteeg, R. & van Nes, J., 4 Apr 2019, In: Nature communications. 10, 1, p. 1530 1530.Research output: Contribution to journal › Article › Academic › peer-review
Open Access78 Citations (Scopus) -
Neuroblastoma is composed of two super-enhancer-associated differentiation states
Van Groningen, T., Koster, J., Valentijn, L. J., Zwijnenburg, D. A., Akogul, N., Hasselt, N. E., Broekmans, M., Haneveld, F., Nowakowska, N. E., Bras, J., Van Noesel, C. J. M., Jongejan, A., Van Kampen, A. H., Koster, L., Baas, F., Van Dijk-Kerkhoven, L., Huizer-Smit, M., Lecca, M. C., Chan, A., Lakeman, A., & 11 others , 1 Aug 2017, In: Nature Genetics. 49, 8, p. 1261-1266 6 p.Research output: Contribution to journal › Article › Academic › peer-review
289 Citations (Scopus)