Please use this identifier to cite or link to this item: https://doi.org/10.1111/cas.14610
Title: Neuroblastoma patient-derived cultures are enriched for a mesenchymal gene signature and reflect individual drug response
Authors: Hee, E.
Wong, M.K.
Tan, S.H.
Choo, Z. 
Kuick, C.H.
Ling, S.
Yong, M.H.
Jain, S.
Lian, D.W.Q.
Ng, E.H.Q.
Yong, Y.F.L.
Ren, M.H.
Syed Sulaiman, N.
Low, S.Y.Y.
Chua, Y.W.
Syed, M.F.
Lim, T.K.H.
Soh, S.Y.
Iyer, P.
Seng, M.S.F.
Lam, J.C.M.
Tan, E.E.K.
Chan, M.Y.
Tan, A.M.
Chen, Y.
Chen, Z. 
Chang, K.T.E.
Loh, A.H.P.
Keywords: cell culture
mesenchymal gene signature
neuroblastoma
patient-derived xenograft
personalized medicine
Issue Date: 2020
Publisher: Blackwell Publishing Ltd
Citation: Hee, E., Wong, M.K., Tan, S.H., Choo, Z., Kuick, C.H., Ling, S., Yong, M.H., Jain, S., Lian, D.W.Q., Ng, E.H.Q., Yong, Y.F.L., Ren, M.H., Syed Sulaiman, N., Low, S.Y.Y., Chua, Y.W., Syed, M.F., Lim, T.K.H., Soh, S.Y., Iyer, P., Seng, M.S.F., Lam, J.C.M., Tan, E.E.K., Chan, M.Y., Tan, A.M., Chen, Y., Chen, Z., Chang, K.T.E., Loh, A.H.P. (2020). Neuroblastoma patient-derived cultures are enriched for a mesenchymal gene signature and reflect individual drug response. Cancer Science 111 (10) : 3780-3792. ScholarBank@NUS Repository. https://doi.org/10.1111/cas.14610
Rights: Attribution-NonCommercial 4.0 International
Abstract: Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, representative primary cultures have been difficult to establish. We developed patient-derived cell cultures (PDCs) from chemo-naïve and post–treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo-response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal-type gene expression signature and showed upregulation of pro-angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard-of-care cytotoxics at human Cmax-equivalent concentrations, MYCN-amplified and non-MYCN-amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients’ responses, and correlated with gene signatures of chemosensitivity. In this translational proof-of-concept study, early-phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug-response testing. © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association
Source Title: Cancer Science
URI: https://scholarbank.nus.edu.sg/handle/10635/197459
ISSN: 13479032
DOI: 10.1111/cas.14610
Rights: Attribution-NonCommercial 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1111_cas_14610.pdf1.15 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons