Search

Background Many countries restrict patient material exchange to central diagnostic laboratories abroad, limiting access to assays like MammaPrint® (MP) and BluePrint® (BP). Both assays are microarray-based, with MP being prognostic for distant recurrence and BP for molecular subtyping of breast cancer (Luminal-, HER2-, and Basal-type). To increase accessibility, decentralization is required with Next Generation Sequencing (NGS) being the preferred testing platform given that most diagnostic laboratories have the technology in place. The aim of this beta testing study is to validate a previously developed and centrally validated MP and BP NGS kit for RNA samples in two large tertiary academic hospitals in Europe. Patients and Methods Patients with early breast cancer diagnosed at the Multidisciplinary Breast Center at University Hospitals Leuven and Curie Institute Paris were prospectively included between September 2017 and January 2018. Patients with bilateral breast cancer or presenting with more than 3 positive lymph nodes were excluded. Only patients with invasive ductal and invasive lobular carcinoma were included. Twenty tissue sections were cut from formalin-fixed, paraffin-embedded (FFPE) blocks; 10 tissue sections were analyzed at the local site using the MP and BP NGS kit, and 10 tissue sections were analyzed at Agendia using the same kit and procedure, as well as with the golden standard method (gene expression microarrays). Targeted RNA sequencing of the 70 MP and 80 BP signature genes was performed on Illumina MiSeq instruments. The raw NGS data generated at the local test sites was sent through a secure file transfer protocol server to Agendia for interpretation and comparison with microarray and NGS performed in the Agendia laboratories. We aimed for a minimum concordance rate between MP and BP outcome of 90% between each local site and Agendia's centralized site. Results In this study, 116 early breast cancer patients were included (73 from University Hospitals Leuven and 43 from Curie Institute). Out of these patients, 52% were MP Low Risk and 48% MP High Risk according to microarray. The patients had a BP luminal, HER2 or basal subtype in respectively 83%, 9% and 8%. Concordance between MP microarray obtained from Agendia and MP NGS obtained from the local sites was 91.4%. Concordance between MP High and Low Risk classification between NGS Leuven versus NGS Agendia was 92.1% and between NGS Curie versus NGS Agendia 95.3%. For BP subtype outcomes, the results from microarray versus NGS for all patients combined from both local sites gave a 98.3% concordance and NGS Agendia versus NGS from each local site gave a 100% concordance. Conclusion The MP and BP NGS kit was successfully validated in a decentralized setting, showing high concordance between results obtained at three different sites. There was a clear benefit of having well-trained NGS experienced diagnostic technical teams. The MP and BP NGS kit the first FFPE targeted RNA sequencing based multigene signature for breast cancer care, will provide a high and equal standard of MP and BP gene expression testing for breast cancer in a decentralized setting. Citation Format: Slembrouck L, Laurent C, Delahaye LJ, Mittempergher L, Vanden Bempt I, Vander Borght S, Darrigues L, Vliegen L, Sintubin P, Raynal V, Bohec M, Reyes C, Rapinat A, Helsmoortel C, Jongen L, Hoste G, Neven P, Wildiers H, Smeets A, Nevelsteen I, Punie K, Van Nieuwenhuysen E, Han S, Salomon AV, Faron EL, Cynober T, Witteveen AT, Neijenhuis S, Glas AM, Reyal F, Floris G. Decentralized beta testing of MammaPrint and BluePrint NGS kit at University Hospitals Leuven and Curie Institute Paris [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-25.

// Guillaume Carita 1,* , Estelle Frisch-Dit-Leitz 2,* , Ahmed Dahmani 1 , Chloe Raymondie 1 , Nathalie Cassoux 3 , Sophie Piperno-Neumann 4 , Fariba Nemati 1 , Cecile Laurent 5 , Leanne De Koning 6 , Ensar Halilovic 7 , Sebastien Jeay 7 , Andrew Wylie 7 , Caroline Emery 7 , Sergio Roman-Roman 2 , Marie Schoumacher 2,* and Didier Decaudin 1,4,* 1 Laboratory of preclinical investigation, Department of Translational Research, PSL University, Institut Curie, Paris, France 2 Department of Translational Research, Institut Curie, PSL University, Paris, France 3 Department of Ophthalmological Oncology, Institut Curie, Paris, France 4 Department of Medical Oncology, Institut Curie, Paris, France 5 Residual Tumor & Response to Treatment Lab, Department of Translational Research, Institut Curie, PSL University, Paris, Paris, France 6 RPPA Platform, Department of Translational Research, Institut Curie, PSL University, Paris, France 7 Novartis Institutes for Biomedical Research, Cambridge, MA USA * These authors have contributed equally to this work Correspondence to: Didier Decaudin, email: // Keywords : xenograft models, cellular response to anticancer drugs, uveal melanoma, AEB071 combinations, synergy Received : April 04, 2016 Accepted : May 10, 2016 Published : May 22, 2016 Abstract Uveal melanoma (UM) is the most common cancer of the eye in adults. Many UM patients develop metastases for which no curative treatment has been identified. Novel therapeutic approaches are therefore urgently needed. UM is characterized by mutations in the genes GNAQ and GNA11 which activate the PKC pathway, leading to the use of PKC inhibitors as a rational strategy to treat UM tumors. Encouraging clinical activity has been noted in UM patients treated with PKC inhibitors. However, it is likely that curative treatment regimens will require a combination of targeted therapeutic agents. Employing a large panel of UM patient-derived xenograft models (PDXs), several PKC inhibitor-based combinations were tested in vivo using the PKC inhibitor AEB071. The most promising approaches were further investigated in vitro using our unique panel of UM cell lines. When combined with AEB071, the two agents CGM097 (p53-MDM2 inhibitor) and RAD001 (mTORC1 inhibitor) demonstrated greater activity than single agents, with tumor regression observed in several UM PDXs. Follow-up studies in UM cell lines on these two drug associations confirmed their combination activity and ability to induce cell death. While no effective treatment currently exists for metastatic uveal melanoma, we have discovered using our unique panel of preclinical models that combinations between PKC/mTOR inhibitors and PKC/p53-MDM2 inhibitors are two novel and very effective therapeutic approaches for this disease. Together, our study reveals that combining PKC and p53-MDM2 or mTORC1 inhibitors may provide significant clinical benefit for UM patients.

Purpose: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from residual tumors to identify efficient chemotherapies and predictive biomarkers in a context of resistance to anthracyclines- and taxanes-based treatments. Experimental Design: PDX were established from residual tumors of primary breast cancer patients treated in neoadjuvant setting. TNBC PDX were treated by anthracyclines, taxanes, platins, and capecitabine. Predictive biomarkers were identified by transcriptomic and immunohistologic analysis. Downregulation of RB1 was performed by siRNA in a cell line established from a PDX. Results: Residual TNBC PDX were characterized by a high tumor take, a short latency, and a poor prognosis of the corresponding patients. With the exception of BRCA1/2-mutated models, residual PDX were resistant to anthracyclines, taxanes, and platins. Capecitabine, the oral prodrug of 5-FU, was highly efficient in 60% of PDX, with two models showing complete responses. Prior treatment of a responder PDX with 5-FU increased expression of thymidylate synthase and decreased efficacy of capecitabine. Transcriptomic and IHC analyses of 32 TNBC PDX, including both residual tumors and treatment-naïve derived tumors, identified RB1 and TYMP proteins as predictive biomarkers for capecitabine response. Finally, RB1 knockdown in a cell line established from a capecitabine-responder PDX decreased sensitivity to 5-FU treatment. Conclusions: We identified capecitabine as efficient chemotherapy in TNBC PDX models established from residual disease and resistant to anthracyclines, taxanes, and platins. RB1 positivity and high expression of TYMP were significantly associated with capecitabine response. Clin Cancer Res; 24(11); 2605–15. ©2018 AACR.

A high percentage of uveal melanoma patients develop metastatic tumors predominantly in the liver. We studied the molecular profiles derived from gene expression microarrays and comparative genomic hybridization microarrays, to identify genes associated with metastasis in this aggressive cancer. We compared 28 uveal melanomas from patients who developed liver metastases within three years of enucleation with 35 tumors from patients without metastases or who developed metastases more than 3 years after enucleation. Protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL3), was identified as a strong predictor of metastasis occurrence. We demonstrated that the differential expression of this gene, which maps to 8q24.3, was not merely a consequence of 8q chromosome overrepresentation. PTP4A3 overexpression in uveal melanoma cell lines significantly increased cell migration and invasiveness in vivo, suggesting a direct role for this protein in metastasis. Our findings suggest that PTP4A3 or its cellular substrates could constitute attractive therapeutic targets to treat metastatic uveal melanomas. Cancer Res; 71(3); 666–74. ©2010 AACR.

Background: triple-negative breast cancer (TNBC) patients with residual disease following neoadjuvant chemotherapy have a high risk of relapse and poor survival. Conventional treatments for relapsed patients are limited, particularly, because standard chemotherapeutic regimens containing anthracyclines and taxanes have usually already been given in the neoadjuvant settings. Our objectives were 1) to identify efficient chemotherapies in patient-derived xenografts (PDX) established from residual TNBC and 2) to determine feasibility of PDX establishment and drug testing before tumor recurrence in patients. Methods: tumors from 51 patients with residual disease at surgery were transplanted in nude mice. Established TNBC PDX were treated with different chemotherapies used in early stages and metastatic settings: anthracyclines combined to cyclophosphamide (AC), taxanes, platins, capecitabine and gemcitabine. Drug responses in PDX were compared to responses in patients who recurred after surgery and were treated in the metastatic setting. Results: overall tumor take of residual tumors was 40% and 75% for TNBC, with 15/20 PDX established, more than twice the tumor take of treatment naïve TNBC (34%). Median latency time, defined as time from implantation till first tumour growth, was only 60 days and was further reduced to 3-4 weeks during successive tumor passages. On the 8 TNBC PDX evaluated for chemosensitivity, 7 exhibited a multidrug-resistance phenotype with resistance or limited response to AC, taxanes and platins. Capecitabine, a chemotherapy given in the advanced stage as second or third line, was efficient in 5 out of 8 PDX tested with 3 models showing stable disease and 2 models durable tumor regressions. Interestingly, capecitabine efficacy was decreased when xenografts were pre-treated with a first line containing platins, suggesting that in some tumors capecitabine might have superior activity when given in the adjuvant setting or as a first line. In one third of TNBC patients, time to recurrence, comprised between 7 and 12 months after surgery, was compatible with xenograft establishment and drug testing. Conclusions and perspectives: we established a unique panel of PDX models from patients with residual disease after neoadjuvant chemotherapy. These aggressive PDX recapitulate the resistance phenotype of patients’ tumors to treatments given in neo-adjuvant and metastatic settings. We identified capecitabine as efficient first line chemotherapy for residual chemoresistant PDX. In 30% of cases, PDX models could have been used to evaluate chemotherapy responses before tumor recurrence occur in patients. In order to identify predictive biomarkers of capecitabine response, additional experiments are ongoing in 25 supplementary TNBC PDX, established from treatment-naïve patients. Citation Format: Elisabetta Marangoni, Cécile Laurent, Florence Coussy, Rania El Botty, Ludmilla de Plater, Franck Assayag, Sophie Vacher, Ivan Bièche, Fabien Reyal. Efficacy of capecitabine in chemoresistant PDX established from triple-negative breast cancers with residual disease after neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3859. doi:10.1158/1538-7445.AM2017-3859

Introduction HER2-positive breast cancer (BC) is a heterogeneous group of aggressive breast cancers, the prognosis of which has greatly improved since the introduction of treatments targeting HER2. However, these tumors may display intrinsic or acquired resistance to treatment, and classifiers of HER2-positive tumors are required to improve the prediction of prognosis and to develop novel therapeutic interventions. Methods We analyzed 2893 primary human breast cancer samples from 21 publicly available datasets and developed a six-metagene signature on a training set of 448 HER2-positive BC. We then used external public datasets to assess the ability of these metagenes to predict the response to chemotherapy (Ignatiadis dataset), and prognosis (METABRIC dataset). Results We identified a six-metagene signature (138 genes) containing metagenes enriched in different gene ontologies. The gene clusters were named as follows: Immunity, Tumor suppressors/proliferation, Interferon, Signal transduction, Hormone/survival and Matrix clusters. In all datasets, the Immunity metagene was less strongly expressed in ER-positive than in ER-negative tumors, and was inversely correlated with the Hormonal/survival metagene. Within the signature, multivariate analyses showed that strong expression of the “Immunity” metagene was associated with higher pCR rates after NAC (OR = 3.71[1.28–11.91], p = 0.019) than weak expression, and with a better prognosis in HER2-positive/ER-negative breast cancers (HR = 0.58 [0.36–0.94], p = 0.026). Immunity metagene expression was associated with the presence of tumor-infiltrating lymphocytes (TILs). Conclusion The identification of a predictive and prognostic immune module in HER2-positive BC confirms the need for clinical testing for immune checkpoint modulators and vaccines for this specific subtype. The inverse correlation between Immunity and hormone pathways opens research perspectives and deserves further investigation.

50% of uveal melanoma patients die from their metastatic disease showing the necessity to develop efficient therapeutic agents and useful and relevant tool for their preclinical assessment. Thus, we have established and characterized an in vivo panel of xenografts directly obtained from patient uveal melanoma tumors. 90 Samples obtained from patient primary tumors or metastases were subcutaneously grafted into SCID mice. 25 patient derived xenografts (PDX) were obtained and 16 have been characterized. UM histology of the PDX was confirmed by pathological analyses. NA17, Tyrosinase, and Melan-A antigen expressions were positive in all samples. Bcl-2 protein was overexpressed in almost all PDX. GNAQ, GNA11 and BAP1 mutations were observed in 4, 10 and 7 of 15 xenografts. The comparison of genomic alterations showed the same DNA damages as the corresponding patients and the differential genes expression observed was mainly due to difference of stroma between patient tumor and PDX. In vivo therapeutic assessments were being performed and will be presented. Our panel of PDX presents the characteristics similar to the patient’s originated tumors and could constitute a useful preclinical tool for testing new agents and protocols.

Background The increasing number of methodologies and tools currently available to analyse gene expression microarray data can be confusing for non specialist users. Findings Based on the experience of biostatisticians of Institut Curie, we propose both a clear analysis strategy and a selection of tools to investigate microarray gene expression data. The most usual and relevant existing R functions were discussed, validated and gathered in an easy-to-use R package (EMA) devoted to gene expression microarray analysis. These functions were improved for ease of use, enhanced visualisation and better interpretation of results. Conclusions Strategy and tools proposed in the EMA R package could provide a useful starting point for many microarrays users. EMA is part of Comprehensive R Archive Network and is freely available at http://bioinfo.curie.fr/projects/ema/.

Purpose: Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice. Experimental Design: Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma. Results: Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents. Conclusions: Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments. Clin Cancer Res; 16(8); 2352–62. ©2010 AACR.

Despite improvements in primary treatment protocols, more than 50% of the patients with uveal melanoma die of late-occurring metastases located in the liver. After diagnosis of metastases the average life expectancy is 6 months and no effective treatment is available at this stage of the disease. Transcriptome analysis linked to comparative genomic hybridization have been used for this particular melanoma to identify a set of genes linked to metastasis that may represent valuable future targets for specific treatments.

Background. There is a lack of evidence documenting the impact of optimized antibiotic use on the rates of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP) in children. This study evaluates the effect of community-based intervention strategies on the prevalence of PNSP colonization Methods. A controlled, population-based pharmacoepidemiological trial was conducted from January through May 2000. Three French geographic areas were selected on the basis of demographic similarities. Two intervention strategies were implemented: (1) reduced antibiotic use, which was achieved by not prescribing antibiotics for presumed viral respiratory tract infections (the prescription-reduction group); and (2) better adaptation of dose and duration (the dose/duration group). A control group received no intervention. The target population was children aged 3-6 years who were attending kindergarten. Oropharyngeal pneumococcus colonization and antibiotic use were monitored throughout the 5-month study. Results. The prescription-reduction, dose/duration, and control groups included 601, 483, and 405 children, respectively. The interventions induced significantly larger decreases in antibiotic use in the prescription-reduction group (-18.8%) and dose/duration group (-17.1%) than in the control group (-3.8%), and the rates of PNSP colonization were initially similar for the 3 groups (52.5%, 55.1%, and 50.0%, respectively). At the end of the 5-month study, the rates of PNSP colonization were 34.5% for the prescription-reduction group (P = .05) and 44.3% for the dose/duration group (P = .8), compared with 46.2% for the control group. Conclusions. Intensive educational strategies aimed at optimizing antibiotic use can significantly reduce the rate of PNSP colonization in areas with high resistance rates.

Uveal melanoma (UM) is the most frequent eye cancer in the adulthood and it represents 4-5% of all melanomas. Although at diagnosis over 95% of patients have disease limited to the eye, about 50% will develop metastases after a median time of three years. From transcriptomic study, we identified PTP4A3/PRL3 level as an efficient predictor of patient's survival. Overexpression of PTP4A3 in UM OCM-1 increased both cell migration and invasiveness. We then got interested in identifying downstream targets of PTP4A3 and more precisely proteins linked to cytoskeleton. We first highlighted collapsin Response Mediator Protein (CRMP2) by 2-D electrophoresis of phosphorus-enriched UM OCM1 stably-expressing PTP4A3 or an inactive catalytic mutant of PTP4A3 (C104S). CRMP2 was dephosphorylated in presence of PTP4A3. CRMP2 expression in UM is inversely correlated with that of PTP4A3, suggesting an antagonistic role of these proteins in tumor progression. Through the use of shRNA in OCM-1, the downregulation of CRMP2 led to an increase in cell migration of PTP4A3-expressing OCM1. In addition, we focused on ATIP3, a protein encoded by the gene MTUS1, which binds to microtubules. In breast cancer, MTUS1 expression was shown to be downregulated in highly proliferative breast carcinomas of poor clinical outcome. Similarly, our transcriptomic analysis showed that expressions of PTP4A3 and MTUS1 were anti-correlated, suggesting that the reduction of MTUS1 gene and ATIP3 expression in UM would be of bad prognosis. In our OCM1 cells, we demonstrated that ATIP3 overexpression blocks proliferation however effect of ATIP3 overexpression on cell migration still need to be elucidaded.In conclusion, CRMP2 and ATIP3 may play a role in the metastatic process of UM tumors expressing high levels of the phosphatase. Citation Format: Geraldine Liot, Oceane Anezo, Cecile Laurent, Selma Maacha, Nathalie Planque, Simon Saule. Potential targets of PTP4A3 involved in uveal melanoma migration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4063. doi:10.1158/1538-7445.AM2014-4063

Background: In HER2 positive and triple-negative breast cancer subgroups, residual disease after neoadjuvant therapy is associated with higher risk of metastatic recurrence compared to patients achieving a pathological complete response. Residual tumor analysis after neoadjuvant treatment is a major and under-explored field to identify resistance mechanisms. To develop patient-derived xenografts (PDX) of residual breast cancer we started a program of residual tumor engraftment in nude mice, following the same procedures previously published for PDX of human breast cancer (Marangoni et al, 2007 and Reyal et al, 2012). Methods: 26 residual breast tumors and 2 residual metastatic axillary lymph nodes were engrafted in swiss nude mice immediately after surgery. Expression of Ki67, HER2, PTEN, P-AKT, P-S6, MET, RET and KIT were analyzed in xenografts by immunohistochemistry, western blot and RT-PCR analyses. Brain, lungs, liver and bones of xenografts were systematically formalin-fixed to search for human metastasis. The in vivo drug response of established xenografts was determined for the following treatments: adryamicin+cyclophosphamide (AC), docetaxel, capecitabine, cisplatin, irinotecan, everolimus, trastuzumab and lapatinib (for the HER2+ PDX). PDX tumors were additionally mechanically dissociated to establish cell lines. Results: Seven PDX were established (tumor take of 25%), 5 triple-negative and 2 HER2+. Six out of seven PDX were metastatic in the lungs. Two xenografts were established from lymph node metastasis. The in vivo drug responses were concordant with the response to neo-adjuvant treatments in patients. Histological analyses showed that xenografts’ tumors recapitulated the patients’ tumor morphology. Residual tumor xenografts expressed high level of Ki67 protein and tumor latency during the first tumor passages was found to be shorter when compared to tumor latency of non pre-treated breast cancers. In 5/5 triple-negative breast cancer PDX the PTEN protein was lost and the PI3 kinase pathway activated. The mTOR inhibitor Everolimus was tested in 2 triple-negative PDX: one was resistant and one was responding, with a tumor growth inhibition of 80%. Triple-negative PDX show expression of “druggable” tyrosin kinase receptors (MET, RET, KIT) providing relevant models to test new target therapies in these models. One cell line was established from a highly metastatic triple-negative breast cancer xenograft. When re-injected into mice, the cell line was tumorigenic, however the tumor architecture was changed and the xenograft was not metastatic. Conclusions: we have established a panel of metastatic PDX models of breast cancer resistant to neo-adjuvant therapies. These models provide a valuable preclinical tool to investigate mechanisms of resistance to neo-adjuvant treatments and for the preclinical testing of new targeted agents. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A9. Citation Format: Elisabetta Marangoni, Dalila Labiod, Franck Assayag, Rania El Botty, Rana Hatem, Sophie Richon, Sophie Chateau-Joubert, Marine Carlus, Hélène Bonsang-Kitzis, Alice Pinheiro, Cécile Laurent, Ivan Bièche, Fabien Reyal. Establishment and characterization of residual breast cancer patient-derived xenografts resistant to neo-adjuvant therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A9.

Objectives. Establishment of pre-clinical models which reflect molecular alterations of primary tumour is a major goal in cancer research. In order to identify novel therapeutic targets and new treatment, xenografts models are powerful tools to analyse pathways and genes involved in carcinogenesis. The aim of this study is to compare gene expression profilings of 4 cancer types (breast, colon, ovary cancer and uveal melanoma) for which primary tumors (PT) and corresponding xenografts (PTDX) are available. We will highlight differentially expressed gene-sets and pathways involved in stromal environment, cancer cells environment, engraftment process and cancer specific development. In addition, this characterisation was associated to survival analysis in breast cancer. Materials and Methods. Gene expression profiling have been determined using Affymetrix technology. Breast cancer dataset was composed of 8 patient/xenograft paired models corresponding to 16 samples, colon, ovary and uveal melanoma datasets was composed of 24, 11 and 12 paired models respectively. Differential analysis between patients and corresponding xenografts was performed on difference matrix (PTDX-PT). Differentially expressed genes were those with a difference unequal to 0. In order to better identified our gene lists, we analysed large public tumors and cell lines datasets. Results. Comparison between PT and corresponding PTDX identified 150 genes always differentially expressed in the different cancer datasets. A large part are down regulated in PTDX. These genes could be divided into two different environments, immunity on one side and angiogenesis, cellular adhesion and development on the other side. Twenty percent are up-regulated and were mainly associated to cell cycle. A large patient and cell lines collections were used for each cancer type in order to differentiate stromal dependant genes and tumor specific genes. A large part of genes were stromal dependant. However some of them presented same expression between patients and cell lines and are lightly deregulated in mice. Survival and response treatment analysis were performed in breast data. In this cancer, genes related to angiogenesis, cellular adhesion and development were associated to survival. Discussion. This descriptive work based on microarray gene-expression profiling allowed to present common genetic background in four different cancer types and increase knowledge in gene micro-environment in carcinogenesis. This study will then focus on breast cancer and we will characterize patient tumors with high probability to grow into mice in order to concentrate on the response to treatment and improve patient management strategies. Citation Format: Cécile Laurent, Elisabetta Marangoni, Philippe Hupé, Fariba Némati, Nathalie Cassoux, David Gentien, Oumou Goundiam, Virginie Dangles-Marie, Sophie Piperno-Neumann, Pascale Mariani, Didier Decaudin, Laurence Desjardins, Xavier Sastre, Sergio Roman-Roman, Fabien Reyal. Identification of gene-expression modifications related to the tumor engraftment in patient-derived xenograft models of solid tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-263. doi:10.1158/1538-7445.AM2013-LB-263