Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein

The emergence and development of gene expression profiling: a key component of the 3B (bench, bedside, bytes) in translational research

National audienceThe emergence and development of gene expression profiling: a key component of the 3B (bench, bedside, bytes) in translational research This paper examines the emergence and development of one of the key components of genomics, namely gene expression profiling. It does so by resorting to computer-based methods to analyze and visualize networks of scientific publications. Our results show the central role played by oncology in this domain, insofar as the initial proof-of-principle articles based on a plant model organism have quickly led to the demonstration of the value of these techniques in blood cancers and to applications in the field of solid tumors, and in particular breast cancer. The article also outlines the essential role played by novel bioinformatics and biostatistical tools in the development of the domain. These computational disciplines thus qualify as one of the three corners (in addition to the laboratory and the clinic) of the translational research triangle

Les réseaux de l’expression génique :Émergence et développement d’un domaine clé de la génomique

International audienceThis paper examines the emergence and development of one of the key components of genomics, namely gene expression profiling. It does so by resorting to computer-based methods to analyze and visualize networks of scientific publications. Our results show the central role played by oncology in this domain, insofar as the initial proof-of-principle articles based on a plant model organism have quickly led to the demonstration of the value of these techniques in blood cancers and to applications in the field of solid tumors, and in particular breast cancer. The article also outlines the essential role played by novel bioinformatics and biostatistical tools in the development of the domain. These computational disciplines thus qualify as one of the three corners (in addition to the laboratory and the clinic) of the translational research triangle.Cet article analyse l’émergence et le développement d’un des domaines clés de la génomique, celui de l’expression génique (gene expression profiling), en utilisant des méthodes d’analyse informatisée et de cartographie du contenu des publications scientifiques. Les résultats de cette analyse détaillent le rôle central joué par l’oncologie dans le développement de ce domaine de recherche. Des démonstrations de principe utilisant un organisme modèle végétal ont rapidement débouché sur des preuves de l’utilité de cette approche dans le cas des hémopathies malignes et des applications dans le domaine des tumeurs solides, notamment les cancers du sein. L’étude met également en relief l’importance de la bioinformatique et des biostatistiques comme conditions de possibilité de ce type de recherches, qui s’imposent dès lors comme le troisième pôle, en plus du laboratoire et de la clinique, du triangle de la recherche translationnelle