Philippe Hupé

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Verified

Philippe verified their affiliation via an institutional email.

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• PhD
• Managing Director at Institut Curie

The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and h...

Importance There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Particip...

Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease, usually in the liver. When metastatic, the prognosis is poor, and few treatment options exist. Here, we investigated the feasibility of establishing patient-derived xenografts (PDXs) from a patient’s tumor in order to scr...

Background: Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome an...

With the advent of high-throughput biotechnological platforms and their ever-growing capacity, life science has turned into a digitized, computational and data-intensive discipline. As a consequence, standard analysis with a bioinformatics pipeline in the context of routine production has become a challenge such that the data can be processed in re...

With the advent of high-throughput biotechnological platforms and their ever-growing capacity, life science has turned into a digitized, computational and data-intensive discipline. As a consequence, standard analysis with a bioinformatics pipeline in the context of routine production has become a challenge such that the data can be processed in re...

The use of a bioinformatics pipeline as a tool to support diagnostic and theranostic decisions in the healthcare process requires the definition of detailed development workflow guidelines. Therefore, we implemented protocols that describe step-by-step all the command lines and actions that the developers have to follow. Our protocols capitalized o...

The use of a bioinformatics pipeline as a tool to support diagnostic and theranostic decisions in the healthcare process requires the definition of detailed development workflow guidelines. Therefore, we implemented protocols that describe step-by-step all the command lines and actions that the developers have to follow. Our protocols capitalized o...

Life science has entered the so-called 'big data era' where biologists, clinicians and bioinformaticians are overwhelmed with high-throughput sequencing data. While they offer new insights to decipher the genome structure they also raise major challenges to use them for daily clinical practice care and diagnosis purposes as they are bigger and bigg...

Life science has entered the so-called 'big data era' where biologists, clinicians and bioinformaticians are overwhelmed with high-throughput sequencing data. While they offer new insights to decipher the genome structure they also raise major challenges to use them for daily clinical practice care and diagnosis purposes as they are bigger and bigg...

The use of a bioinformatics pipeline as a tool to support diagnostic and theranostic decisions in the healthcare process requires the definition of detailed development workflow guidelines. Therefore, we implemented protocols that describe step-bystep all the command lines and actions that the developers have to follow. Our protocols capitalized on...

Life science has entered the so-called ’big data era’ where biologists, clinicians and bioinformaticians are overwhelmed with unprecedented amount of data. High-throughput sequencing has revolutionized genomics and offers new insights to decipher the genome structure. However, using these data for daily clinical practice care and diagnosis purposes...

The analytic platform described in this chapter uses proteins extracted from cultured cells as an infinite source of material to set up, validate, and quality control an RPPA platform. Readout of the arrays uses near-infrared fluorescence labeling and data normalization is performed using the bioinformatics package NormaCurve.In the first part, we...

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin mi...

Cell-cell communication involves a large number of molecular signals that function as words of a complex language whose grammar remains mostly unknown. Here, we describe an integrative approach involving (1) protein-level measurement of multiple communication signals coupled to output responses in receiving cells and (2) mathematical modeling to un...

Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular a...

Next-generation sequencing (NGS) is routinely used for constitutional genetic analysis. However, cross-contamination between samples constitutes a major risk that could impact the results of the analysis. We have developed ART-DeCo, a tool using the allelic ratio (AR) of the Single Nucleotide Polymorphisms sequenced with regions of interest. When a...

Cervical cancer (CC) is the fourth most common cause of cancer deaths in women worldwide, for which prognostic and predictive biomarkers are largely lacking. RAIDs is a EU-funded project on cervical cancer that spans seven European countries. The main objective of the RAIDs project is to use this tumor type, which is easily accessible for repeated...

Background and purpose: Online delineation workshops (ODW) permit training of geographically dispersed participants. The purpose is to evaluate the methodology of an ODW using FALCON to harmonize delineation within a European multicentre trial on locally advanced cervical cancer (LACC). Material and methods: Two ODW included 46 clinicians (14 ce...

L’oncologie est aujourd’hui intimement liée au numérique, et ce, aussi bien pour les activités de recherche que pour les soins. Ce mariage est issu avant tout de notre capacité à explorer la dimension moléculaire des cellules grâce au séquençage de leur génome. Les mutations mises en évidence sont dès lors autant de cibles thérapeutiques potentiell...

Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of t...

Supplementary Figures 1-7 and Supplementary Table 1

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality worldwide. CC pathogenesis is triggered when human papillomavirus (HPV) inserts into the genome, resulting in tumour suppressor gene inactivation and oncogene activation. Collecting tumour and blood samples is critical for identifying these genetic...

Background Recent retrospective data1,2 identified major molecular alterations in cervical cancer (CC), but so far there has been no prospective assessment on patient outcome using a complete molecular profiling with quality control evaluation of treatment. The Cetuxicol (phase 2) clinical trial showed that the addition of Cetuximab over a 6 week p...

Aims: The aim of this study was to analyse a series of borderline and malignant phyllodes tumours (PTs) of the breast by whole-genome profiling to identify genomic markers that could help to recognise potentially malignant tumours within borderline tumours. Methods: We evaluated the genetic imbalances of a series of 53 PTs (30 borderline, 23 mal...

Background Cervical cancer (CC) is -second to breast cancer- a dominant cause of gynecological cancer-related deaths worldwide. CC tumor biopsies and blood samples are of easy access and vital for the development of future precision medicine strategies. Design BIO-RAIDs is a prospective multicenter European study, presently recruiting patients in...

Cells adapt to their environment through the integration of complex signals. Multiple signals can induce synergistic or antagonistic interactions, currently considered as homogenous behaviours. Here, we use a systematic theoretical approach to enumerate the possible interaction profiles for outputs measured in the conditions 0 (control), signals X,...

The treatment of epithelial ovarian cancer (EOC) is narrowly focused despite the heterogeneity of this disease in which outcomes remain poor. To stratify EOC patients for targeted therapy, we developed an approach integrating expression and genomic analyses including the BRCAness status. Gene expression and genomic profiling were used to identify g...

The availability of high-throughput technologies and their application makes them very attractive for cancer centers offering new opportunities through new clinical tools for daily practice. However, establishing such a clinical facility is not a trivial task due to the complexity of PM framework along with the overwhelming amount of data. From the...

Most molecularly targeted agents (MTAs) are expected to work in subgroups of cancer patients characterized by the presence of molecular alterations in the tumor cells. However, clinical development is generally carried out according to tumor type. The SHIVA randomized trial on the contrary has been set up to investigate which of tumor biology or tu...

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤500 ms) of radiation de...

Motivation: Because of its low cost, amplicon sequencing, also known as ultra-deep targeted sequencing, is now becoming widely used in oncology for detection of actionable mutations, i.e. mutations influencing cell sensitivity to targeted therapies. Amplicon sequencing is based on the polymerase chain reaction amplification of the regions of intere...

Precision medicine in oncology is becoming reality thanks to the next-generation sequencing of tumours and the development of targeted inhibitors enabling tailored therapies. Many clinical trials base their strategy on the identification of mutations to deliver the targeted inhibitor that counteract supposedly the effect of a mutated gene. Recent r...

Precision medicine (PM) requires the delivery of individually adapted medical care based on the genetic characteristics of each patient and his/her tumor. The last decade witnessed the development of high-throughput technologies such as microarrays and next-generation sequencing which paved the way to PM in the field of oncology. While the cost of...

Background: The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. Results of the feasibility study on the first 100 enrolled patients are presented. Methods: Adult patients with a...

Inactivation of the NF2 gene predisposes to neurofibromatosis type II and the development of schwannomas. In vitro studies have shown that loss of NF2 leads to the induction of mitogenic signaling mediated by receptor tyrosine kinases (RTKs), MAP kinase, AKT, or Hippo pathways. The goal of our study was to evaluate the expression and activity of th...

Array-CGH can be used to determine DNA copy number, imbalances in which are a fundamental factor in the genesis and progression of tumors. The discovery of classes with similar patterns of array-CGH profiles therefore adds to our understanding of cancer and the treatment of patients. Various input data representations for array-CGH, dissimilarity m...

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 expressio...

We have previously developed a new method for the development and maintenance of uveal melanoma (UM) xenografts in immunodeficient mice. Here, we compare the genetic profiles of the primary tumors to their corresponding xenografts that have been passaged over time. The study included sixteen primary UMs and corresponding xenografts at very early (P...

Telomere shortening is a major source of chromosome instability (CIN) at early stages during carcinogenesis. However, the mechanisms through which telomere-driven CIN (T-CIN) contributes to the acquisition of tumor phenotypes remain uncharacterized. We discovered that human epithelial kidney cells undergoing T-CIN display massive microRNA (miR) exp...

Cancer is a complex and heterogeneous disease that exhibits high levels of robustness against various therapeutic interventions. It is a constellation of diverse and evolving disorders that are manifested by the uncontrolled proliferation of cells that may eventually lead to fatal dysfunction of the host system. Although some of the cancer subtypes...

Neither the molecular mechanisms whereby cancer cells intrinsically are or become resistant to the DNA-damaging agent cisplatin nor the signaling pathways that account for cisplatin cytotoxicity have thus far been characterized in detail. In an attempt to gain further insights into the molecular cascades elicited by cisplatin (leading to resistance...

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular gluta...

Acute leukemias are characterized by deregulation of transcriptional networks that control the lineage specificity of gene expression. The aberrant overexpression of the Spi-1/PU.1 transcription factor leads to erythroleukemia. To determine how Spi-1 mechanistically influences the transcriptional program, we combined a ChIP-seq analysis with transc...

Reverse phase protein array (RPPA) is a powerful dot-blot technology that allows studying protein expression levels as well as post-translational modifications in a large number of samples simultaneously. Yet, correct interpretation of RPPA data has remained a major challenge for its broad-scale application and its translation into clinical researc...

Reproductibility of control arrays. (PDF)

Observed intensities on a control array (no primary antibody) for the dilution series of the BSA+chk2 samples with five different starting concentrations (0.8, 0.9, 1, 1.1 and 1.2 mg/ml). The ctrl array distinguishes between the different starting concentrations. (TIF)

For a Chk2-labeled array, mean intensities were plotted against the Coefficient of Variation for all samples and all dilution steps. Note that high CVs are associated with low intensities. (TIF)

Observed intensities on a Sypro Ruby stained array for the dilution series of the BSA+chk2 samples with five different starting concentrations (0.8, 0.9, 1, 1.1 and 1.2 mg/ml). The sypro array correctly distinguishes between the different starting concentrations. (TIF)

CV criterion, regression criterion and correlation coefficient of the ModelSC 1 for the five arrays stained with anti-Chk2. (TIF)

Comparison of the ModelSC1, 2, 3 and 4 for the five arrays stained with anti-Chk2. (TIF)

The interplay between allergy and autoimmunity has been a matter of long debate. Epidemiologic studies point to a decreased frequency of allergy in patients with autoimmune diseases. However, recent studies suggest that IL-17 and related cytokines, which play a central role in autoimmunity, might also promote allergy. To address this controversy, w...

A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expr...

2 arrayCGH class 2 3 flag class 3 3.1 Attributes........................................ 3

DNA methylation is a major epigenetic modification in human cells. Illumina HumanMethylation27 BeadChip makes it possible to quantify the methylation state of 27 578 loci spanning 14 495 genes. We developed a non-parametric normalization method to correct the spatial background noise in order to improve the signal-to-noise ratio. The prediction per...

DNA methylation is a major epigenetic modification in human cells. Illumina HumanMethylation27 BeadChip makes it possible to quantify the methylation state of 27 578 loci spanning 14 495 genes. We developed a non-parametric normalization method to correct the spatial background noise in order to improve the signal-to-noise ratio. The prediction per...

Random X inactivation represents a paradigm for monoallelic gene regulation during early ES cell differentiation. In mice, the choice of X chromosome to inactivate in XX cells is ensured by monoallelic regulation of Xist RNA via its antisense transcription unit Tsix/Xite. Homologous pairing events have been proposed to underlie asymmetric Tsix expr...

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 deve...

In the degradative pathway, the progression of cargos through endosomal compartments involves a series of fusion and maturation events. The HOPS (homotypic fusion and protein sorting) complex is part of the machinery that promotes the progression from early to late endosomes and lysosomes by regulating the exchange of small GTPases. We report that...

R scripts applied to the breast cancer gene expression dataset [18]. R script used to analyse the breast cancer gene expression data set [18].

EMA vignette. The vignette discuss the detailed biological/clinical analysis strategy used at Institut Curie and presents an application to a gene expression dataset.

The increasing number of methodologies and tools currently available to analyse gene expression microarray data can be confusing for non specialist users. 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 an...

The multistage process of cancer formation is driven by the progressive acquisition of somatic mutations. Replication stress creates genomic instability in mammals. Using a well-defined multistep leukemia model driven by Spi-1/PU.1 overexpression in the mouse and Spi-1/PU.1-overexpressing human leukemic cells, we investigated the relationship betwe...

To investigate whether integration of HPV DNA in cervical carcinoma is responsible for structural alterations of the host genome at the insertion site, a series of 34 primary cervical carcinomas and eight cervical cancer-derived cell lines were analysed. DNA copy number profiles were assessed using the Affymetrix GeneChip Human Mapping 250K Sty arr...

Accumulation of extrachromosomal DNA molecules (double minute) is often responsible for gene amplification in cancers, but the mechanisms leading to their formation are still largely unknown. By using quantitative PCR, chromosome walking, in situ hybridization on metaphase chromosomes and whole genome analysis, we studied a glioma containing four e...

MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes, including proliferation and apoptosis. We used microarray technology to identify miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre-miRNAs) per se were not leth...

T helper 17 (Th17) cells produce IL-17 but can also make tumor necrosis factor, interleukin (IL)-6, IL-10, IL-21, and IL-22. These cytokines collectively contribute to the functional outcome of the Th response. IL-22 plays a critical role in some Th17-associated diseases, such as psoriasis, but its relationship to IL-17 remains controversial. Here,...

Incurable metastases develop in approximately 50% of patients with uveal melanoma (UM). The purpose of this study was to analyze genomic profiles in a large series of ocular tumors and liver metastases and design a genome-based classifier for metastatic risk assessment. A series of 86 UM tumors and 66 liver metastases were analyzed by using a BAC C...

Basal-like carcinomas (BLCs) and human epidermal growth factor receptor 2 overexpressing (HER2+) carcinomas are the subgroups of breast cancers that have the most aggressive clinical behaviour. In contrast to HER2+ carcinomas, no targeted therapy is currently available for the treatment of patients with BLCs. In order to discover potential therapeu...

A PDF containing figures showing the expression of HER2 measured by Western blotting and its correlation with RPPA data. Figure a illustrates the expression of total HER2 protein expression measured by Western blotting in human BLCs and HER2+ carcinomas. P value (*** p < 0.001) is represented (Mann-Whitney test). Figure b illustrates the correlatio...

A PDF containing a figure showing that the active form of Akt is detected in tumour cells within the biopsies by immunohistochemistry. Expression and localisation of phospho-Akt (S473), and hence activated Akt, was analysed on TMA in BLCs and HER2+ carcinomas. Phospho-Akt showed low, medium and high expression depending on the tumour samples. Phosp...

A PDF containing a figure that illustrates recurrent genomic alterations around PTEN locus in human basal-like breast cancers. Genomic analysis using the VAMP software (Visualization and Analysis of array-CGH, transcriptome and other Molecular Profiles) [60] around the PTEN gene (between 80,676,000 and 98,604,000 bp of chromosome 10) are shown for...

A PDF containing figures showing Akt activation in basal-like breast cancer measured by Western blotting and its correlation with RPPA data. Figures a, b and c illustrate the expression of total Akt, the phosphorylated/active form of Akt (phospho-Akt (S473)), and the activity of Akt determined as the 'phospho/total' ratio, respectively, in human BL...

A PDF containing a figure that validates the PTEN-dependent activation of Akt observed by RPPA in basal-like cancer with Western blot technology. Figure a shows PTEN protein level. Data are representative of two separate experiments. Figure b indicates the correlation between RPPA and Western blotting analysis for PTEN protein expression. Figure c...

Cancer is a major cause of death and lots of effort must be made to defeat the disease. Microarray technology is a powerful tool very helpful in oncology in order to better understand the molecular mechanisms involved in tumoral progression. We know that cancer is due to a modification of the gene regulation. Then, the study of gene expression in t...

Purpose Current therapeutic efforts in Uveal Melanoma are directed toward detection of liver metastases at an earlier stage and adjuvant systemic therapy in high risk patients. Beside clinical and histological features, specific cytogenetic alterations, particularly monosomy 3 and gain of 8q, are strongly associated with metastasis. Methods A serie...