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3 results on '"Laetitia Gaston"'

1. Medium levels of transcription and replication related chromosomal instability are associated with poor clinical outcome

Author

Ataaillah Benhaddou, Laetitia Gaston, Gaëlle Pérot, Nelly Desplat, Laura Leroy, Sophie Le Guellec, Mohamed Ben Haddou, Philippe Rochaix, Thibaud Valentin, Gwenaël Ferron, Christine Chevreau, Binh Bui, Eberhard Stoeckle, Axel Le Cesne, Sophie Piperno-Neumann, Françoise Collin, Nelly Firmin, Gonzague De Pinieux, Jean-Michel Coindre, Jean-Yves Blay, and Frédéric Chibon

Subjects
Medicine, Science
Abstract

Abstract Genomic instability (GI) influences treatment efficacy and resistance, and an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP “hotspotness” magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (transcription-associated chromosomal instability index) and iRACIN (replication-associated chromosomal instability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in Leiomyosarcoma (LMS) and that they may be combined to form a new classifier called MAGIC (mixed transcription- and replication-associated genomic instability classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.

Published
2021
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2. Molecular characterization of a series of 990 index patients with albinism

Author

Vincent Michaud, Claudio Plaisant, Caroline Rooryck, Fanny Morice-Picard, Eulalie Lasseaux, Didier Lacombe, Benoit Arveiler, Laetitia Gaston, Perrine Pennamen, Aurélien Trimouille, and Solene Monfermé

Subjects
Male, 0301 basic medicine, Albinism, Dermatology, Disease, Biology, General Biochemistry, Genetics and Molecular Biology, DNA sequencing, 03 medical and health sciences, medicine, Humans, Allele, Alleles, Hypopigmentation, Gene Rearrangement, Genetics, Comparative Genomic Hybridization, Genetic heterogeneity, High-Throughput Nucleotide Sequencing, medicine.disease, Hypoplasia, 030104 developmental biology, Molecular Diagnostic Techniques, Oncology, Female, medicine.symptom, Comparative genomic hybridization
Abstract

Albinism is a clinically and genetically heterogeneous disease characterized by variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity impedes the establishment of phenotype-genotype correlations. To obtain a precise diagnosis, we screened the 19 known albinism genes in 990 index patients using targeted next-generation sequencing (NGS) and high-resolution comparative genomic hybridization. A molecular diagnosis was obtained in 72.32% of patients. A total of 243 new pathogenic variants were identified. Intragenic rearrangements represented 10.8% of all pathogenic alleles. NGS panel analysis allowed establishing a diagnosis for the rarest forms of the disease, which could not be diagnosed otherwise. Because of the clinical overlap between the different forms of the disease, diagnosis nowadays clearly relies on molecular grounds.

Published
2018

3. Confirmation and Expansion of the Phenotype Associated with the Recurrent p.Val837Met Variant in TRPM3

Author

Aurélien Trimouille, Jean-Madeleine de Sainte Agathe, Eulalie Lasseaux, Didier Lacombe, Benoit Arveiler, Virginie Raclet, Jerome Aupy, Laetitia Gaston, Claudio Plaisant, Julien Van-Gils, and Clémence Pfirrmann

Subjects
Genetics, Epilepsy, business.industry, Intellectual disability, medicine, Missense mutation, General Medicine, medicine.disease, business, Phenotype, Genetics (clinical)
Abstract

Dyment et al. (2019) recently reported eight novel patients with intellectual disability and epilepsy associated with heterozygous de novo missense variants in TRPM3. We report a novel patient with the same recurrent de novo missense of TRPM3 found in seven of these eight cases, p.(Val837Met), providing an emphasis towards ocular and joints defects along with a non-mandatory epilepsy.

Published
2020

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