A5012837083- Cancer Genomics and Diagnostics
- Evolution and Genetic Dynamics
- Mathematical Biology Tumor Growth
- Thyroid Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Renal cell carcinoma treatment
- vaccines and immunoinformatics approaches
- Radiomics and Machine Learning in Medical Imaging
- Lymphoma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Vascular Tumors and Angiosarcomas
- Computational Drug Discovery Methods
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Hedgehog Signaling Pathway Studies
- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Single-cell and spatial transcriptomics
- Advanced Breast Cancer Therapies
Université de Strasbourg
2021-2022
University of California, San Diego
2017-2021
Moores Cancer Center
2016-2021
Centre National de la Recherche Scientifique
2016-2020
Institut Gustave Roussy
2012-2020
San Diego Supercomputer Center
2017
Inserm
2016
Stabilité génétique et oncogenèse
2014
Université Paris-Sud
2014
Bicêtre Hospital
2007
Purpose Fusions that involve neurotrophic-tropomyosin receptor kinase ( NTRK) genes are known drivers of oncogenesis. Therapies target these ultra-rare, constitutionally active NTRK fusions have been remarkably effective. Herein, we analyze the prevalence full array alterations—fusions, mutations, copy number alterations, and increased transcript expression—in diverse adult pediatric tumor types to understand landscape aberrations in cancer. Methods We assessed 13,467 samples available from...
Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, physicians from multiple specialties) tumor board (MTB), which included project manager facilitate obtaining clinical-grade...
Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), 2 (PDCD1LG2 PDL2), and Janus kinase (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting high response rates to (PD-1)/programmed (PD-L1) blockade. The prevalence utility of PDL1 amplification as a biomarker PD-1/PD-L1 blockade are unknown other tumors.To examine the its solid tumors.This retrospective study (October 1, 2012, October 2017) used deidentified tumor database from commercial company...
Medullary thyroid carcinoma (MTC) is characterized by proto-oncogene RET mutations in almost all hereditary cases as well more than 40% of sporadic cases. Recently, a high prevalence RAS was reported MTC, suggesting an alternative genetic event MTC tumorigenesis.This study aimed to extend this observation screening somatic mutational status RET, BRAF, and the three proto-oncogenes large series patients with MTC.Direct sequencing (exons 8, 10, 11, 13, 14, 15, 16), BRAF 11 15), KRAS, HRAS,...
Abstract Purpose: Liquid biopsies based on circulating cell-free DNA (cfDNA) analysis are described as surrogate samples for molecular analysis. We evaluated the concordance between tumor (tDNA) and cfDNA a large cohort of patients with advanced or metastatic solid tumor, eligible phase I trial good performance status, enrolled in MOSCATO 01 (clinical NCT01566019). Experimental Design: Blood were collected at inclusion was extracted from plasma 334 patients. Hotspot mutations screened using...
Tumor-associated neo-antigens are mutated peptides that allow the immune system to recognize affected cell as foreign. Cells carrying excessive mutation load often develop mechanisms of tolerance. PD-L1/PD-1 checkpoint immunotherapy is a highly promising approach overcome these protective signals and induce tumor shrinkage. Yet, nature driving those beneficial responses remains unclear. Here, we show APOBEC-related mutagenesis – mechanism at crossroads between anti-viral immunity endogenous...
Immunotherapy with checkpoint inhibitors, such as antibodies blocking the programmed cell-death receptor-1 (PD-1), has resulted in remarkable responses patients having traditionally refractory cancers. Although response to PD-1 inhibitors correlates ligand (PD-L1 or PD-L2) expression, positivity represents only a part of predictive model necessary for selecting predisposed respond immunotherapy. We used all genomic, transcriptomic, proteomic and phenotypic data related 8,475 pan-cancer...
Hydrophobic neoantigens are more immunogenic because they better presented by the major histocompatibility complex and recognized T cells. Tumor cells can evade immune response expressing checkpoints such as programmed death ligand 1. Checkpoint blockade reactivates recognition be effective in diseases melanoma, which harbors a high tumor mutational burden (TMB). Cancers presenting low or intermediate TMB also respond to checkpoint blockade, albeit less frequently, suggesting need for...
Metastatic basal cell cancer (BCC) is an ultra-rare malignancy with no approved therapies beyond Hedgehog inhibitors. We characterized the genomics, tumor mutational burden (TMB), and anti-PD-1 therapy responses in patients locally advanced or metastatic BCC. Overall, 2,039 diverse samples that had undergone comprehensive genomic profiling (CGP) were reviewed. Eight advanced/metastatic BCC identified (two two CGP analyses; total, 10 biopsies). Two tumors demonstrated PD-L1 amplification....
Abstract Background Angiosarcoma is an aggressive tumor. Recent case series describe exceptional responses to checkpoint blockade in this disease. Methods Herein, we explored the genomic correlates of 48 angiosarcomas from Project (12,499 variants analyzed 6603 genes; whole-exome sequencing) versus 10,106 pan-cancer tumors The Cancer Genome Atlas including 235 sarcomas but no angiosarcoma. Results At molecular level, were heterogeneous. Those located face and scalp presented high tumor...
Anti-angiogenic therapies are an important class of anti-cancer treatment drugs. However, their efficacy is limited to certain tumors and would benefit from identifying a biomarker predictive therapeutic response. TP53 (tumor protein p53) tumor suppressor gene frequently mutated in cancer implicated cell-cycle regulation, apoptosis, angiogenesis. Data 7,525 unique samples (representing 30 cohorts) were retrieved the TCGA database analyze relationship between TP53-mutation status VEGFA...
Plasma cell-free DNA (cfDNA) is emerging as an important diagnostic tool in cancer. However, cfDNA alterations may differ from those tissue and sometimes reflect processes unrelated to the cancer, including clonal hematopoiesis (CH). We examined plasma cfDNA, tested by next-generation sequencing (NGS), for characterized (excluding variants of unknown significance) 135 patients with invasive glioma. Overall, 21% (28/135) had ≥1 alteration; 17% (23/135) CH-type mutations. Temozolomide (a...
Advanced medullary thyroid cancers (MTCs) are now being treated with drugs that inhibit receptor tyrosine kinases, many of which involved in angiogenesis. Response rates vary widely, and toxic effects common, so treatment should be reserved for MTCs likely to responsive these drugs. RET mutations common MTCs, but it is unclear how they influence the microvascularization tumors. We examined 45 germ-line or somatic (RETmut group) 34 wild-type (RETwt). Taqman Low-Density Arrays were used assess...
Abstract Predicting oncologic outcome is challenging due to the diversity of cancer histologies and complex network underlying biological factors. In this study, we determine whether machine learning (ML) can extract meaningful associations between clinical trial, drug‐related biomarker molecular profile information. We analyzed therapeutic trials corresponding 1102 outcomes from 104 758 patients with advanced colorectal adenocarcinoma, pancreatic melanoma nonsmall‐cell lung cancer. For each...
Metastatic cancer is a medical challenge that has been historically resistant to treatments. One area of leverage in care the development molecularly-driven combination therapies, offering possibility overcome resistance. The selection optimized treatments based on complex molecular features patient’s tumor may be rendered easier by using computer-assisted program. We used PreciGENE® platform uses multi-pathway analysis identify personalized therapeutic options. These options are ranked...
The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E mutation described to be associated with a worse prognostic carcinomas, as well extrathyroidal invasion and increased mortality.To our knowledge, there are no reported studies neither from Morocco nor other Maghreb countries regarding the prevalence in carcinomas. Here we aim evaluate frequency oncogene Moroccan carcinomas.In this Single-Institution retrospective study realized Anatomic Pathology Histology...
Eosinophilic cystitis is a rare manifestation of hypereosinophilia and cause morbidity, including dysuria hematuria. Although some cases can be attributed to infection or allergy, most are assessed idiopathic treated with corticosteroids. However, also due actionable clonal molecular alterations in the haematopoietic cells, similar other myeloproliferative neoplasms. Common mutations associated eosonophilic syndromes platelet-derived growth factor receptor α β c-kit, though pathogenic have...
Determining the status of HER2‐neu amplification and overexpression in breast cancer is crucial for prognosis but mostly treatment purposes. Standard techniques include determination IHC combination with situ hybridization to confirm a case IHC2+ using either core‐needle biopsy or surgical specimen. qPCR has been also demonstrated be able determine HER2 status, core biopsies specimens. Fine‐needle aspiration reliable, quicker less invasive technique that widely used diagnosis cancer. In this...
Abstract Background Precision-medicine initiatives are driven by the molecular analysis of tumor samples (fresh or FFPE material). Such an approach is limited availability material and challenges related to on-purpose biopsies. A very appealing alternative advance precision-medicine development liquid biopsies using cfDNA. Methods We investigated use NGS on biopsy plasma, evaluated consistency between tissue (tDNA) cfDNA a prospective cohort patients with metastatic locally advanced solid...