Dépistage du cancer du sein

The purpose of this article is to remind why and how the screening mammographic program has been developed in France, and generalized in 2004, and to explain what is the BI-RADS of ACR. Perspectives on emerging new technologies that may change breast cancer screening will be discussed.     

Génétique moléculaire des dysgénésies testiculaires

The first step of male differentiation is the testis determination which is genetically controled. The key role of SRY gene is now established. However, a number of clinical and genetic data favoured the role of other genes taking place upstream or downstream SRY. Most of 46, XX males possess a translocated SRY gene and thus develop testis, but SRY gene is not found in 10% of such patients. Likewise, the molecular study of 46, XY females participated in the identification of SRY as testis determining factor, but 80% of XY gonadal dysgenesis are not explained by an abnormality of SRY gene. Several clinical situations permitted to suspect the role of autosomal (chromosome 1, 9, 10 17 …) and X chromosome loci in the pathology of sex determination. Some recent works concern, in particular, the testis determining factor of the X chromosome (TDF-X) that could act as a repressor of the testis differentiation. In conclusion, molecular mechanisms of sexual determination appear to be much complex, involving probably several genes in a pathway that remain to be elucidated.     

Anticorps anti-spermatozoïdes: techniques de dépistage et interprétation des résultats

Since the first publication on the detection of sperm-agglutinating antibodies in infertile men, multiple assays have been described. The most useful tests are able to detect antibodies bound to the sperm membrane of motile spermatozoa. The immunobeads test (IBT) is considered to be the most advantageous in terms of its sensitivity, the low incidence of false-positive results, and its ability to localize antibodies of different immunoglobulin classes on the sperm surface. The IBT assay can be used in parallel with the mixed antiglobulin reaction (MAR), to detect sperm-associated antibodies in the ejaculates of infertile men, the most rational way to test for antisperm antibodies (ASA) in males. In view of the high level of agreement between the two assays, MAR, the easier of the two, may be used as a first step in the detection of these antibodies. A positive MAR must be confirmed by IBT, as this assay is more specific for the detection of IgA antibodies. The clinical significance of sperm-associated antibodies is usually established according to the proportion of motile spermatozoa coated with immunobeads, its class and its localization on the sperm surface. However, binding of immunobeads does not provide any information about the antigens against which the antibodies are directed. As the functional effects of sperm-associated antibodies may vary as a function of their antigenic specificities, other assays, using purified fertilization related antigens, are necessary to establish, for each individual, the specific impact of the antibodies on the fertilization process. The indirect IBT assay has recently become the most widely used test to detect the various classes of ASA in serum and cervical mucus of infertile women and in the serum and seminal fluid of infertile men, in combination with the direct assay described above. However, in most laboratories, it is performed with only one dilution of the biological fluid tested, usually a low dilution, so that antibody levels of no significance for fertility could be detected. This may explain a recente debate (Human Reprod, 1999) on the significance of ASA as a cause of infertility. At present, and in the absence of standardized assays able to identify the antigens involved in each individual immune reaction, antibody assays, as detected by the IBT assay, in the serum and/or genital secretions of infertile subjects might provide useful clinical guidance.     

Dépistage de la trisomie 21 par les marqueurs sériques

Jusqu’ au milieu des années 80, la seule stratégie de dépistage consistait à proposer une amniocentèse aux femmes agées de 38 ans et plus. Puis, les progrès liés au développement de l’échographie ont permis de révéler des malformations fœtales, ce qui a ouvert la voie au dépistage des anomalies chromosomiques chez les femmes plus jeunes. Enfin, la mise en évidence de marqueurs biochimiques dans le sérum maternel au 2^ème trimestre de la grossesse a conduit à une extension du dépistage de la trisomie 21 à toutes les femees enceintes quel que soit leur age, que le fœtus présente ou non des malformations visibles à l’échographie.     

Techniques de recherche des polymorphismes génétiques

Sequencing the human genome has allowed the discovery of millions of DNA sequence variants. Sequence variations in human DNA are mainly present asSingle Nucleotide Polymorphisms (SNPs); this common form of variation is found about once every 1,000 bases in the human genome and 1.8 million SNPs have now been identified and located. The accessibility of databases of SNPs opens the possibility of studying the influence of these polymorphisms on disease risks as well as on drug responses. Numerous approaches have been set up for the identification of SNPs. In this review we describe the main techniques used for the identification of these polymorphisms. They rely on two major consequences of sequence variations: the apparition or the disappearance of restriction enzyme sites or the alteration of DNA strand hybridization due to the presence of a mismatch. Southern blotting and restriction endonucleases have allowed the development of the technique ofrestriction fragment length polymorphisms (RFLPs), now performed on PCR products. Several other approaches such as denaturing high-performance liquid chromatography or real-time PCR can detect allele differences upon re-hybridization and heteroduplex formation. However, DNA sequencing remains the obligate step for the positive identification of known or unknown SNPs. At last, the development of high-throughput methods allows a large increase in the rate of discovery of SNPs likely.