Universität zu Köln

van Wezel, Esther M., van Zogchel, Lieke M. J., van Wijk, Jalenka, Timmerman, Ilse, Vo, Ngoc-Kim, Zappeij-Kannegieter, Lily, DeCarolis, Boris, Simon, Thorsten, van Noesel, Max M., Molenaar, Jan J., van Groningen, Tim, Versteeg, Rogier, Caron, Huib N., van der Schoot, C. Ellen, Koster, Jan, van Nes, Johan and Tytgat, Godelieve A. M. (2019). Mesenchymal Neuroblastoma Cells Are Undetected by Current mRNA Marker Panels: The Development of a Specific Neuroblastoma Mesenchymal Minimal Residual Disease Panel. JCO Precis. Oncol., 3. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 2473-4284

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Abstract

PURPOSE Patients with neuroblastoma in molecular remission remain at considerable risk for disease recurrence. Studies have found that neuroblastoma tissue contains adrenergic (ADRN) and mesenchymal (MES) cells; the latter express low levels of commonly used markers for minimal residual disease (MRD). We identified MES-specific MRD markers and studied the dynamics of these markers during treatment. PATIENTS AND METHODS Microarray data were used to identify genes differentially expressed between ADRN and MES cell lines. Candidate genes were then studied using real-time quantitative polymerase chain reaction in cell lines and control bone marrow and peripheral blood samples. After selecting a panel of markers, serial bone marrow, peripheral blood, and peripheral blood stem cell samples were obtained from patients with high-risk neuroblastoma and tested for marker expression; survival analyses were also performed. RESULTS PRRX1, POSTN, and FMO3 mR NAs were used as a panel for specifically detecting MES mRNA in patient samples. MES mRNA was detected only rarely in peripheral blood; moreover, the presence of MES mRNA in peripheral blood stem cell samples was associated with low event-free survival and overall survival. Of note, during treatment, serial bone marrow samples obtained from 29 patients revealed a difference in dynamics between MES mRNA markers and ADRN mRNA markers. Furthermore, MES mRNA was detected in a higher percentage of patients with recurrent disease than in those who remained disease free (53% v 32%, respectively; p= .03). CONCLUSION We propose that the markers POSTN and PRRX1, in combination with FMO3, be used for real-time quantitative polymerase chain reaction-based detection of MES neuroblastoma mRNA in patient samples because these markers have a unique pattern during treatment and are more prevalent in patients with poor outcome. Together with existing markers of MRD, these new markers should be investigated further in large prospective studies. (C) 2019 by American Society of Clinical Oncology

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Wezel, Esther M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Zogchel, Lieke M. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Wijk, Jalenka UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmerman, Ilse UNSPECIFIED UNSPECIFIED UNSPECIFIED Vo, Ngoc-Kim UNSPECIFIED UNSPECIFIED UNSPECIFIED Zappeij-Kannegieter, Lily UNSPECIFIED UNSPECIFIED UNSPECIFIED DeCarolis, Boris UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED van Noesel, Max M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Molenaar, Jan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Groningen, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Versteeg, Rogier UNSPECIFIED UNSPECIFIED UNSPECIFIED Caron, Huib N. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Schoot, C. Ellen UNSPECIFIED UNSPECIFIED UNSPECIFIED Koster, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED van Nes, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Tytgat, Godelieve A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-131430
DOI:	10.1200/PO.18.00413
Journal or Publication Title:	JCO Precis. Oncol.
Volume:	3
Date:	2019
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	2473-4284
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLYMERASE-CHAIN-REACTION; HIGH-RISK NEUROBLASTOMA; BONE-MARROW; MOLECULAR RESPONSE; QRT-PCR; RT-PCR; CANCER; TRANSITION; EXPRESSION; CHILDREN Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13143