A5049240411- Ocular Oncology and Treatments
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Nanoplatforms for cancer theranostics
- Cutaneous Melanoma Detection and Management
- Nonmelanoma Skin Cancer Studies
- Retinal Development and Disorders
- Chromatin Remodeling and Cancer
- Hippo pathway signaling and YAP/TAZ
- Cancer Immunotherapy and Biomarkers
- Ear and Head Tumors
- Cell Adhesion Molecules Research
- Corneal Surgery and Treatments
- Reconstructive Facial Surgery Techniques
- Angiogenesis and VEGF in Cancer
- Bladder and Urothelial Cancer Treatments
- Ubiquitin and proteasome pathways
- Central Venous Catheters and Hemodialysis
- Advanced Fluorescence Microscopy Techniques
- Cardiac tumors and thrombi
- DNA Repair Mechanisms
- Hedgehog Signaling Pathway Studies
- Axon Guidance and Neuronal Signaling
Institut Curie
2016-2024
Université Paris Sciences et Lettres
2018-2023
Inserm
2020-2023
Centre Oscar Lambret
2023
École Nationale Supérieure des Mines de Paris
2023
La Ligue Contre le Cancer
2020-2021
Hôpital Européen
2014
Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present metastatic patient an exceptional high sensitivity to PD-1 inhibitor associated outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic inactivation in the tumor. We identify additional tumors The Cancer Genome Atlas (TCGA) cohorts similar hypermutator profiles patients carrying mutations loss heterozygosity. This MBD4-related phenotype may explain unexpected responses...
Disruption of splicing patterns due to mutations genes coding factors in tumors represents a potential source tumor neoantigens, which would be both public (shared between patients) and tumor-specific (not expressed normal tissues). In this study, we show that the factor SF3B1 uveal melanoma generate such immunogenic neoantigens. Memory CD8+ T cells specific for these neoantigens are preferentially found 20% patients with bearing SF3B1-mutated tumors. Single-cell analyses neoepitope-specific...
Up to 50% of uveal melanomas (UM) metastasise the liver within 10 years diagnosis, and these almost always prove rapidly fatal. As histopathological growth patterns (HGPs) metastases replacement desmoplastic type, particularly from colon breast carcinoma, may import valuable biological prognostic information, we have studied HGP in a series 41 UM originating patients period 2006-2017. Twenty underwent enucleation while 21 had radiation therapy. Analysis by array comparative genomic...
Uveal melanoma (UM) arises from malignant transformation of melanocytes in the uveal tract eye. This rare tumor has a poor outcome with frequent chemo-resistant liver metastases. BAP1 is only known predisposing gene for UM. UMs are generally characterized by low mutation burden, but some display high level CpG>TpG mutations associated MBD4 inactivation. Here, we explored incidence germline variants consecutive series 1093 primary UM case patients and 192 tumors monosomy 3 (M3).We performed...
Uveal melanoma (UM) is the most common cancer of eye. The loss chromosome 3 (M3) associated with a high risk metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting other tumor types in which T cell infiltration correlates better prognosis. Whether these cells represent an antitumor response and how would be primed eye both unknown. Herein, we characterized infiltrating primary UMs. CD8+ Treg were abundant D3 tumors. CD39+PD-1+CD8+...
Abstract Purpose: Uveal melanomas (UM) are genetically simple tumors carrying few copy number alterations (CNA) and a low mutation burden, except in rare MBD4-deficient, hypermutated cases. The genomics of uveal melanoma metastatic progression has not been described. We assessed the genetic heterogeneity primary MBD4-proficient -deficient melanomas. Experimental Design: prospectively collected 75 16 samples from 25 consecutive patients, performed whole-exome sequencing. Results: contained...
High throughput molecular screening techniques allow the identification of multiple alterations, some which are actionable and can be targeted by molecularly agents (MTA). We aimed at evaluating relevance using this approach in frame Institut Curie Molecular Tumor Board (MTB) to guide patients with cancer clinical trials MTAs.We included all presented MTB from 4 October 2014 31 2017. The following information was extracted chart: decision perform tumour profiling, types analyses, samples...
// Marick Laé 1 , Sophie Gardrat 1, 2 Rondeau Camille Richardot Martial Caly Walid Chemlali Vacher Jérôme Couturier Odette Mariani Philippe Terrier 3 Ivan Bièche Service de Pathologie, Institut Curie, 75248 Paris Cedex 05, France Génétique, Unité pharmacogénomique, Gustave Roussy, 94805, Villejuif Cedex, Correspondence to: Laé, email: marick.lae@curie.fr Keywords: MED12, phyllodes tumors Received: April 15, 2016 Accepted: October 13, Published: 31, ABSTRACT Exome sequencing has recently...
Uveal Melanoma (UM) is a rare and malignant intraocular tumor with dismal prognosis. Even if radiation or surgery permit an efficient control of the primary tumor, up to 50% patients subsequently develop metastases, mainly in liver. The treatment UM metastases challenging patient survival very poor. most recurrent event activation Gαq signaling induced by mutations GNAQ/11. These activate downstream effectors including protein kinase C (PKC) mitogen-activated kinases (MAPK). Clinical trials...
Studies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but prognosis UMs with partial deletion chromosome 3 remains to be defined.To examine association in metastasis-free survival.This retrospective cohort study 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, July 31, 2015, assessed patients presenting without loss at a referral center. Data analysis was September 2017, November 30, 2017.Uveal melanoma or...
We report here the results of a prospective study circulating tumor DNA (ctDNA) detection in patients undergoing uveal melanoma (UM) liver metastases resection (NCT02849145).
Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults, exerting high metastatic potential and poor prognosis. Histone deacetylases (HDACs) play a key role carcinogenesis, HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents clinical settings. The aim of this study was to evaluate significance HDAC-1, -2, -4, -6 expression UM. examined immunohistochemically 75 UM tissue specimens correlated with tumors' clinicopathological...
Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied correlation with etiological factors. collected 47 primary samples performed next-generation sequencing 400 genes. Hotspot mutations in
Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases associated with a poor prognosis. Ephrine receptors (Eph) are largest subpopulation tyrosine kinase receptors. They play an important role processes related to formation and progression cancer. aim study was evaluate expression ephrin EphA1, EphA5, EphA7 uveal its associations clinicopathological parameters, overall survival, disease-free survival. included 94 previously...
To evaluate the prognostic implications of melanin quantification assessed by magnetic resonance imaging (MRI) with respect to clinical, pathological, and genetic features liver metastases uveal melanoma (LMUM). This single-center retrospective cohort study included 63 patients eligible for margin-free resection LMUM between 2007 2018. Comparative genomic hybridization resected on microarrays was performed risk classification. Metastases exhibiting monosomy 3 any type gain chromosome 8...
Background: Uveal melanoma is the most common primary intraocular malignancy in adults. In advanced cases, prognosis very poor. Thus far, no effective methods of pharmacotherapy this cancer have been found. The aim study was to evaluate expression PARP-1, best-known member family poly(ADP-ribose) polymerases, uveal and its associations with clinicopathological parameters, overall survival, disease-free survival. Methods: included 91 patients who underwent enucleation due melanoma. PARP-1...
Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease, usually liver. When metastatic, prognosis poor, and few treatment options exist. Here, we investigated feasibility establishing patient-derived xenografts (PDXs) from a patient’s tumor order screen for therapies that patient could benefit from. Samples obtained 29 tumors liver metastases uveal were grafted into SCID mice. PDX models successfully established 35% 67%...
Ocular medulloepithelioma (ME) is a rare congenital tumor which occurs usually during childhood but also reported in adults. They have seen an intraocular 89 years-old female with history of small cell lung carcinoma. Transscleral fine needle aspiration was performed. Aspirates were rich and composed two distinctive populations cells. The first consisted epithelioid large cohesive cells rosettes. Nuclei oval chromatin delicate nucleoli. second population smaller dispersed regular nuclei...