- van Groningen Tim, Koster Jan, Valentijn Linda J., Zwijnenburg Danny A., Akogul Nurdan, Hasselt Nancy E., Broekmans Marloes, Haneveld Franciska, Nowakowska Natalia E., Bras Johannes, van Noesel Carel J. M., Jongejan Aldo, van Kampen Antoine H., Koster Linda, Baas Frank, van Dijk-Kerkhoven Lianne, Huizer-Smit Margriet, Lecca Maria C., Chan Alvin, Lakeman Arjan, Molenaar Piet, Volckmann Richard, Westerhout Ellen M., Hamdi Mohamed, van Sluis Peter G., Ebus Marli E., Molenaar Jan J., Tytgat Godelieve A., Westerman Bart A., van Nes Johan, Versteeg Rogier Neuroblastoma is composed of two super-enhancer-associated differentiation states Nature genetics 2017;49 (8):1261-1266 [PubMed]
- Valentijn Linda J., Koster Jan, Zwijnenburg Danny A., Hasselt Nancy E., van Sluis Peter, Volckmann Richard, van Noesel Max M., George Rani E., Tytgat Godelieve A. M., Molenaar Jan J., Versteeg Rogier TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nature genetics 2015;47 (12):1411-+ [PubMed]
- Eleveld Thomas F., Oldridge Derek A., Bernard Virginie, Koster Jan, Daage Leo Colmet, Diskin Sharon J., Schild Linda, Bentahar Nadia Bessoltane, Bellini Angela, Chicard Mathieu, Lapouble Eve, Combaret Valérie, Legoix-Né Patricia, Michon Jean, Pugh Trevor J., Hart Lori S., Rader JulieAnn, Attiyeh Edward F., Wei Jun S., Zhang Shile, Naranjo Arlene, Gastier-Foster Julie M., Hogarty Michael D., Asgharzadeh Shahab, Smith Malcolm A., Guidry Auvil Jaime M., Watkins Thomas B. K., Zwijnenburg Danny A., Ebus Marli E., van Sluis Peter, Hakkert Anne, van Wezel Esther, van der Schoot C. Ellen, Westerhout Ellen M., Schulte Johannes H., Tytgat Godelieve A., Dolman M. Emmy M., Janoueix-Lerosey Isabelle, Gerhard Daniela S., Caron Huib N., Delattre Olivier, Khan Javed, Versteeg Rogier, Schleiermacher Gudrun, Molenaar Jan J., Maris John M. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations Nature genetics 2015;47 (8):864-871 [PubMed]
- Molenaar Jan J., Koster Jan, Zwijnenburg Danny A., van Sluis Peter, Valentijn Linda J., van der Ploeg Ida, Hamdi Mohamed, van Nes Johan, Westerman Bart A., van Arkel Jennemiek, Ebus Marli E., Haneveld Franciska, Lakeman Arjan, Schild Linda, Molenaar Piet, Stroeken Peter, van Noesel Max M., Ora Ingrid, Santo Evan E., Caron Huib N., Westerhout Ellen M., Versteeg Rogier Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012;483 (7391):589-U107 [PubMed]
- Versteeg Rogier CANCER Tumours outside the mutation box Nature 2014;506 (7489):438-439 [PubMed]
Prof. PhD R. Versteeg (Regulatory networks in cancer)
The research program focuses on the elucidation of the regulatory networks underlying pathogenesis of the childhood tumors neuroblastoma, medulloblastoma and rhabdomyosarcoma. Affymetrix profiling was performed on large series of these tumors. Genes with a role in these tumors are systematically switched on or switched off in cell lines by inducible cDNA or siRNA expression (Tet-on system). RNA from time-courses of these cell lines was analyzed by Affymetrix expression arrays, usually in triplo and of different clones. Downstream pathways of about 15 genes were analyzed in this way. Elaborate bioinformatics programs were generated to identify downstream networks of the manipulated genes and to relate these data to the expression patterns observed in the tumor series. As each of the manipulated genes (like MYCN, NOTCH, EZH2, MSX1, CDK2) appear to regulate expression of hundreds of downstream genes, the emerging networks appear to be complex. The networks are further analyzed by silencing of transcription factors and other key genes in the networks. This requires an increase in the number of gene manipulations. For this purpose we have started to silence gene expression by lentivirally encoded siRNAs (TRC library). Over 15 genes were efficiently silenced this way and their downstream pathways are currently analyzed by microarrays.
Theme: Oncology
Faculty
PhD J.J.B. Koster
PhD L.J. Valentijn
Postdocs
PhD M. Hamdi
PhD W.J. van Nes
PhD E.M. Westerhout
Others
P. Molenaar
BEng D.A. Zwijnenburg
Prof. MD PhD H.N. Caron (Paediatric Oncology; biology and clinical)
- M.C. Commandeur
- A. Hakkert
- AMC
- Europese Unie
- KWF Kankerbestrijding
- ZonMw