Ovarian Carcinoma Patient Derived Xenografts Reproduce Their Tumor of Origin and Preserve an Oligoclonal Structure
Open accessAbstract
// Pierre-Emmanuel Colombo 1,2 , Stanislas du Manoir 2,3 , Béatrice Orsetti 2,3,4 , Rui Bras-Gonçalves 2,3,4 , Mario B. Lambros 5 , Alan MacKay 5 , Tien-Tuan Nguyen 2,3 , Florence Boissière 6 , Didier Pourquier 7 , Frédéric Bibeau 7 , Jorge S. Reis-Filho 8 and Charles Theillet 2,3 1 Department of Surgical Oncology, Institut de Cancérologie de Montpellier, Montpellier, France 2 Institut de Recherche en Cancérologie de Montpellier, Université Montpellier, Montpellier, France 3 INSERM U1194, Montpellier, France 4 Institut de Cancérologie de Montpellier, Montpellier, France 5 Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK 6 Unité de Recherche Translationnelle, Institut de Cancérologie de Montpellier, Montpellier, France 7 Department of Pathology, Institut de Cancérologie de Montpellier, Montpellier, France 8 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Charles Theillet, email: // Jorge Reis-Filho, email: // Keywords : ovarian cancer, PDX, CNC, mutations, oligoclonality Received : April 10, 2015 Accepted : July 02, 2015 Published : July 31, 2015 Abstract Advanced Epithelial Ovarian Cancer (EOC) patients frequently relapse by 24 months and develop resistant disease. Research on EOC therapies relies on cancer cell lines established decades ago making Patient Derived Xenografts (PDX) attractive models, because they are faithful representations of the original tumor. We established 35 ovarian cancer PDXs resulting from the original graft of 77 EOC samples onto immuno-compromised mice. PDXs covered the diversity of EOC histotypes and graft take was correlated with early patient death. Fourteen PDXs were characterized at the genetic and histological levels. PDXs reproduced phenotypic features of the ovarian tumors of origin and conserved the principal characteristics of the original copy number change (CNC) profiles over several passages. However, CNC fluctuations in specific subregions comparing the original tumor and the PDXs indicated the oligoclonal nature of the original tumors. Detailed analysis by CGH, FISH and exome sequencing of one case, for which several tumor nodules were sampled and grafted, revealed that PDXs globally maintained an oligoclonal structure. No overgrowth of a particular subclone present in the original tumor was observed in the PDXs. This suggested that xenotransplantation of ovarian tumors and growth as PDX preserved at least in part the clonal diversity of the original tumor. We believe our data reinforce the potential of PDX as exquisite tools in pre-clinical assays.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The major advantage of using PDX models is the ability to reproduce histology of the human tumor.
“The major advantage of using PDX models is the ability to reproduce histology of the human tumor (Colombo et al., 2015)”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Colombo et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Integrated genomic analyses of ovarian carcinoma
Perou, C. M. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/hvp3-wg08 · Cited by 7,927 · see citing works
Mutational landscape and significance across 12 major cancer types
Kandoth, C., McLellan, M. D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J. F., Wyczalkowski, M. A., et al. (2013) · Nature · doi:10.1038/nature12634 · Cited by 4,419 · see citing works
Evaluating cell lines as tumour models by comparison of genomic profiles
Domcke, S., Sinha, R., Levine, D. A., Sander, C., & Schultz, N. D. (2013) · Nature Communications · doi:10.1038/ncomms3126 · Cited by 1,426 · see citing works
Ledermann, J. A., Raja, F. A., Fotopoulou, C., González-Martı́n, A., Colombo, N., & Sessa, C. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt333 · Cited by 1,102 · see citing works
DeRose, Y. S., Wang, G., Lin, Y.-C., Bernard, P. S., Buys, S. S., Ebbert, M., Factor, R. E., Matsen, C. B., Milash, B. A., Nelson, E. W., et al. (2011) · Nature Medicine · doi:10.1038/nm.2454 · Cited by 1,006 · see citing works
Cannistra, S. (1993) · New England Journal of Medicine · doi:10.1056/nejmra041842 · Cited by 957 · see citing works
Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity
Marusyk, A., Tabassum, D. P., Altrock, P. M., Almendro, V., Michor, F., & Polyák, K. (2014) · Nature · doi:10.1038/nature13556 · Cited by 588 · see citing works
Pathogenesis of Ovarian Cancer
Kurman, R. J., & Shih, I. (2008) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0b013e318161e4f5 · Cited by 460 · see citing works
A New Model of Patient Tumor-Derived Breast Cancer Xenografts for Preclinical Assays
Marangoni, E., Vincent‐Salomon, A., Auger, N., Degeorges, A., Assayag, F., de Crémoux, P., de Plater, L., Guyader, C., Pinieux, G. D. B. D., Judde, J., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0078 · Cited by 423 · see citing works
An In vivo Platform for Translational Drug Development in Pancreatic Cancer
Rubio‐Viqueira, B., Jimeno, A., Cusatis, G., Zhang, X., Iacobuzio–Donahue, C. A., Karikari, C. A., Shi, C., Danenberg, K. D., Danenberg, P. V., Kuramochi, H., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0113 · Cited by 414 · see citing works
Bashashati, A., Ha, G., Tone, A. A., Ding, J., Prentice, L., Roth, A. J. L., Rosner, J., Shumansky, K., Kalloger, S. E., Senz, J., et al. (2013) · The Journal of Pathology · doi:10.1002/path.4230 · Cited by 413 · see citing works
New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact
Levanon, K., Crum, C., & Drapkin, R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.1107 · Cited by 412 · see citing works
Hidalgo, M. M., Bruckheimer, E. M., Rajeshkumar, N. V., Garrido‐Laguna, I., Oliveira, E. D., Rubio‐Viqueira, B., Strawn, S. J., Wick, M. J., Martell, J., & Sidransky, D. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0233 · Cited by 406 · see citing works
Clonogenic assay with established human tumour xenografts
Fiebig, H., Maier, A., & Burger, A. M. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.01.009 · Cited by 290 · see citing works
Fichtner, I., Rolff, J., Soong, R., Hoffmann, J., Hammer, S., Sommer, A., Becker, M., & Merk, J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0138 · Cited by 286 · see citing works
Shaw, T. J., Senterman, M. K., Dawson, K. M., Crane, C. A., & Vanderhyden, B. C. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.08.013 · Cited by 278 · see citing works
Villarroel, M. C., Rajeshkumar, N. V., Garrido‐Laguna, I., Jesus‐Acosta, A. D., Jones, S., Maitra, A., Hruban, R. H., Eshleman, J. R., Klein, A. P., Laheru, D. A., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0893 · Cited by 249 · see citing works
Bolton, K., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S., Karlan, B., Lambrechts, D., Despierre, E., Barrowdale, D., McGuffog, L., et al. (2012) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2012.20 · Cited by 219 · see citing works
Molecular profiling of patient-derived breast cancer xenografts
Reyal, F., Guyader, C., Decraene, C., Lucchesi, C., Auger, N., Assayag, F., de Plater, L., Gentien, D., Poupon, M., Cottu, P. H., et al. (2012) · Breast Cancer Research · doi:10.1186/bcr3095 · Cited by 192 · see citing works
Tumorgrafts as In Vivo Surrogates for Women with Ovarian Cancer
Weroha, S. J., Becker, M. A., Enderica-Gonzalez, S., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2611 · Cited by 189 · see citing works
Sensitivity and resistance to treatment in the primary management of epithelial ovarian cancer
Colombo, P., Fabbro, M., Theillet, C. G., Bibeau, F., Rouanet, P., & Ray-Coquard, I. L. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.08.017 · Cited by 188 · see citing works
Self-citationDong, X., Guan, J., English, J. C., Flint, J., Yee, J., Evans, K. G., Murray, N., MacAulay, C. E., Ng, R. T., Gout, P. W., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2878 · Cited by 188 · see citing works
Colombo, N., Peiretti, M., Parma, G., Lapresa, M., Mancari, R., Carinelli, S. G., Sessa, C., & Castiglione, M. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq244 · Cited by 185 · see citing works
John, T., Kohler, D. M., Pintilie, M., Yanagawa, N., Pham, N., Li, M., Panchal, D., Hui, F., Meng, F., Shepherd, F. A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2224 · Cited by 176 · see citing works
Némati, F., Sastre‐Garau, X., Laurent, C., Couturier, J., Mariani, P., Desjardins, L., Piperno-Neumann, S., Lantz, O. J., Asselain, B. J. R., Plancher, C., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3066 · Cited by 165 · see citing works
Tumor Mutation Burden Forecasts Outcome in Ovarian Cancer with BRCA1 or BRCA2 Mutations
Birkbak, N. J., Kochupurakkal, B. S., Izarzugaza, J. M. G., Eklund, A. C., Li, Y., Liu, J. F., Szállási, Z., Matulonis, U. A., Richardson, A. L., Iglehart, J. D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080023 · Cited by 141 · see citing works
Topp, M. D., Hartley, L., Cook, M., Heong, V. Y. M., Boehm, E., McShane, L., Pyman, J. M., McNally, O., Ananda, S. S., Harrell, M., et al. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.01.008 · Cited by 137 · see citing works
Integrated genomic analyses of ovarian carcinoma
The Cancer Genome Atlas Research Network (2011) · Nature · doi:10.1038/nature10166 · Cited by 129 · see citing works
Charafe‐Jauffret, E., Ginestier, C., Bertucci, F., Cabaud, O., Wicinski, J., Finetti, P., Josselin, E., Adélaı̈de, J., Nguyen, T.-T., Monville, F., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4704 · Cited by 128 · see citing works
Self-citationDobbin, Z. C., Katre, A. A., Steg, A. D., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2373 · Cited by 118 · see citing works
Colombo, P. E., Mourrégot, A., Fabbro, M., et al. (2008) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2008.01.005 · Cited by 114 · see citing works
Self-citationMattie, M., Christensen, A., Chang, M. S., Yeh, W., Said, S., Shostak, Y., Capo, L., Verlinsky, A., An, Z., Joseph, I. B. J., et al. (2013) · Neoplasia · doi:10.1593/neo.13922 · Cited by 100 · see citing works
Modeling of response to endocrine therapy in a panel of human luminal breast cancer xenografts
Cottu, P. H., Marangoni, E., Assayag, F., de Crémoux, P., Vincent‐Salomon, A., Guyader, C., de Plater, L., Ganem‐Elbaz, C., Karboul, N., Fontaine, J. J., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1815-5 · Cited by 96 · see citing works
Patient-derived breast tumor xenografts facilitating personalized cancer therapy
Landis, M. D., Lehmann, B. D., Pietenpol, J. A., et al. (2013) · Breast Cancer Research · doi:10.1186/bcr3355 · Cited by 91 · see citing works
du Manoir, S., Orsetti, B., Bras-Gonçalves, R., Nguyen, T.-T., Lasorsa, L., Boissière‐Michot, F., Massemin, B., Colombo, P., Bibeau, F., Jacot, W., et al. (2013) · Molecular Oncology · doi:10.1016/j.molonc.2013.11.010 · Cited by 72 · see citing works
Self-citationKaram, J. A., Zhang, X.-Y., Tamboli, P., Margulis, V., Wang, H., Abel, E. J., Culp, S. H., & Wood, C. G. (2010) · European Urology · doi:10.1016/j.eururo.2010.11.043 · Cited by 61 · see citing works
Petrillo, L. A., Wolf, D. M., Kapoun, A. M., et al. (2012) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2226-y · Cited by 44 · see citing works
Patient-Derived Xenograft Models in Gynecologic Malignancies
Scott, C. L., MacKay, H. J., & Haluska, P. (2014) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2014.34.e258 · Cited by 37 · see citing works
Némati, F., Daniel, C., Arvelo, F. A., Legrier, M., Froget, B., Livartowski, A., Assayag, F., Bourgeois, Y., Poupon, M., & Decaudin, D. (2009) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e3283300a29 · Cited by 33 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mieulet, V., Garnier, C., Kieffer, Y., Guilbert, T., Nemati, F., Marangoni, E., Renault, G., Chamming’s, F., Vincent-Salomon, A., & Mechta-Grigoriou, F. (2021) · Scientific Reports · doi:10.1038/s41598-021-83685-0 · Cited by 79 · see citing works
Yee, C., Dickson, K.-A., Muntasir, M. N., Ma, Y., & Marsh, D. J. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.836984 · Cited by 66 · see citing works
- Authors
- Colombo, P.-E., du Manoir, S., Orsetti, B., Bras-Gonçalves, R., Lambros, M. B., MacKay, A., Nguyen, T.-T., Boissière, F., Pourquier, D., Bibeau, F., Reis-Filho, J. S., & Theillet, C.
- Affiliations
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Institut de Recherche en Cancérologie de Montpellier, Université Montpellier, Montpellier, France
- Inserm (FR)
- Institute of Cancer Research (GB)
- Unité de Recherche Translationnelle, Institut de Cancérologie de Montpellier, Montpellier, France
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2015-07-31
- Volume
- 6
- Issue
- 29
- Pages
- 28327-28340
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4695063
- OpenAlex
- W1845067222
- Cited by
- 34
- References
- 39
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- patient-derived xenografts, epithelial ovarian cancer, copy number alterations, oligoclonality, tumor heterogeneity, tumor evolution, clonal evolution, histological subtypes, tumor recurrence, graft take, tumor microenvironment, tumor stroma, tumor-infiltrating immune cells, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, tumor-infiltrating neutrophils, tumor-infiltrating dendritic cells, tumor-infiltrating T cells, tumor-infiltrating B cells, tumor-infiltrating NK cells, tumor-infiltrating myeloid cells, tumor-infiltrating Treg cells, tumor-infiltrating Th1 cells
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Clone Cells, Female, Humans, Mice, Nude, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Ovarian Neoplasms, Prognosis, Transplantation, Heterologous, Gene Expression Regulation, Neoplastic, Survival Analysis, Gene Expression Profiling, Heterografts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
