Raphaël Leman
A5080616088- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- BRCA gene mutations in cancer
- RNA Research and Splicing
- RNA modifications and cancer
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Genetic factors in colorectal cancer
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Radio Frequency Integrated Circuit Design
- Hemodynamic Monitoring and Therapy
- Prostate Cancer Treatment and Research
- Advancements in Semiconductor Devices and Circuit Design
- CRISPR and Genetic Engineering
- Endometrial and Cervical Cancer Treatments
- Probabilistic and Robust Engineering Design
- Cancer Cells and Metastasis
- Nuclear Structure and Function
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Plant Virus Research Studies
- Uterine Myomas and Treatments
- Sarcoma Diagnosis and Treatment
Centre François Baclesse
2018-2025
Normandie Université
2018-2025
Inserm
2018-2025
Centre François Baclesse
2022-2025
Onco Lille
2024-2025
Université de Caen Normandie
2018-2024
Génomique du cancer et du cerveau
2024
Université de Rouen Normandie
2018-2022
Institut de Cancérologie de l'Ouest
2019-2020
Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
2019
Abstract Variant interpretation is the key issue in molecular diagnosis. Spliceogenic variants exemplify this as each nucleotide variant can be deleterious via disruption or creation of splice site consensus sequences. Consequently, reliable silico prediction spliceogenicity would a major improvement. Thanks to an international effort, set 395 studied at mRNA level and occurring 5′ 3′ regions (defined 11 14 bases surrounding exon/intron junction, respectively) was collected for different...
Modeling splicing is essential for tackling the challenge of variant interpretation as each nucleotide variation can be pathogenic by affecting pre-mRNA via disruption/creation motifs such 5′/3′ splice sites, branch or regulatory elements. Unfortunately, most in silico tools focus on a specific type motif, which why we developed Splicing Prediction Pipeline (SPiP) to perform, one single bioinformatic analysis based machine learning approach, comprehensive assessment effect different motifs....
Branch points (BPs) map within short motifs upstream of acceptor splice sites (3'ss) and are essential for splicing pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR RNABPS were developed during the last decade. Here, we evaluated their capability to detect position BPs, also predict impact on variants occurring 3'ss.We used a large set constitutive alternative human 3'ss collected from Ensembl (n = 264,787 3'ss) in-house...
Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict variant's impact on needed interpret the growing number variants unknown significance (VUS) identified by exome genome sequencing. Here, we present results CAGI6 Splicing VUS challenge, invited predictions 56 ascertained clinically functionally validated determine impact. The performance 12 prediction methods, along with SpliceAI CADD,...
The optimal application of maintenance PARP inhibitor therapy for ovarian cancer requires accessible, robust, and rapid testing homologous recombination deficiency (HRD). However, in many countries, access to HRD is problematic the failure rate high. We developed an academic test support treatment decision-making.Genomic Instability Scar (GIScar) was through targeted sequencing a 127-gene panel determine status. GIScar trained from noninterventional study with 250 prospectively collected...
There is an urgent need of precision medicine for ovarian cancer patients to identify who respond chemotherapy and PARP inhibitors, a therapy targeting homologous recombination deficiency (HRD). Here we established panel 37 long-term patient-derived tumor organoids (PDTO) models various histological subtypes from 224 demonstrated that they mimic the molecular characteristics original tumors. Screening chemotherapeutic drugs showed PDTO exhibit heterogeneous responses, response high-grade...
Background PALB2 monoallelic loss-of-function germ-line variants confer a breast cancer risk comparable to the average BRCA2 pathogenic variant. Recommendations for reduction strategies in carriers are similar. Elaborating robust criteria identify PALB2— without incurring overprediction—is thus of paramount clinical relevance. Towards this aim, we have performed comprehensive characterisation alternative splicing , analysing its relevance classification truncating and splice site according...
Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the with margin healthy tissue. Especially if complete not possible, radiation therapy chemotherapy are used conjunction surgery, but generally low efficiency. Ongoing researches focused on understanding genetic molecular basis chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments more effective. goal this study evaluate...
<h3>Introduction/Background</h3> UTOLA assessed the efficacy of Parp-inhibitor for advanced/M+ EC pts without progression after 1st line platinum CT and to analyse in some molecular subgroups. <h3>Methodology</h3> is a 2/1 randomized, double-blind, placebo controlled, phase IIb trial, comparing olaparib maintenance (ola, 300 mg po BID) vs (pl) until or intolerance with stratification on P53, MMR status, response previous CT. Primary endpoint was PFS ITT. Main secondary endpoints were...
Abstract Background Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development chemoresistance. Despite emergence PARP inhibitors, which have revolutionized therapeutic management some these ovarian cancers, 5-year overall survival rate remains around 45%. Therefore, it crucial develop new strategies, identify predictive biomarkers and predict response treatments. In this context, functional assays based on patient-derived tumor models could...
Modeling splicing is essential for tackling the challenge of variant interpretation as each nucleotide variation can be pathogenic by affecting pre-mRNA via disruption/creation motifs such 5’/3’ splice sites, branch sites or regulatory elements. Unfortunately, most in silico tools focus on a specific type motif, which why we developed Splicing Prediction Pipeline (SPiP) to perform, one single bioinformatic analysis based machine learning approach, comprehensive assessment effect different...
Introduction: DNA damage repair genes are altered in 20–35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination (HRR) deficiency. These alterations could also predict platinum sensitivity. Although carboplatin was inconclusive unselected mCRPC, the literature suggests an anti-tumoral mCRPC HHR gene alterations. We aimed...
At least 10% of the BRCA1/2 tests identify variants uncertain significance (VUS) while distinction between pathogenic (PV) and benign (BV) remains particularly challenging. As a typical tumor suppressor gene, inactivation second wild-type (WT) BRCA1 allele is expected to trigger cancer initiation. Loss heterozygosity (LOH) WT most frequent mechanism for biallelic inactivation. To evaluate if LOH can be an effective predictor variant pathogenicity, we carried out analysis on DNA extracted...
Alternative splicing is an important biological process widely analyzed in molecular diagnostic settings. Indeed, a variant can be pathogenic by alteration and suspected (e.g. truncating variant) rescued splicing. In this context, detecting quantifying alternative challenging. We developed SpliceLauncher, fast easy to use open source tool that aims at detecting, annotating splice junctions high resolution.SpliceLauncher available https://github.com/raphaelleman/SpliceLauncher.Supplementary...
<h3>Introduction/Background</h3> High-grade serous ovarian cancers with deficiency of homologous recombination DNA repair (HRD) are sensitive to the combination bevacizumab and olaparib as maintenance therapy in PAOLA-1 trial (NCT02477644). HRD status is determined by mutational scars within tumor genome. Here, we developed a new method called GIScar (Genomic Instability Scar) suitable most academic molecular biology laboratory constraints. <h3>Methodology</h3> We used sequencing data from...
Abstract Background: Branch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR RNABPS were developed during the last decade. Here, we evaluated their capability to detect position BPs, also predict impact on variants occurring 3’ss. Results: We used a large set constitutive alternative human 3’ss collected from...