Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Caractérisation de la capture du VIH-1 (du récepteur DC-SIGN aux extensions trans-épithéliales des cellules dendritiques)

En tant que sentinelles du système immunitaire, les CD expriment une lectine, le DC-SIGN, présentant une forte affinité pour de nombreux pathogènes, incluant le VIH-1. L objectif premier de cette étude est d utiliser cette lectine comme outil de screening d enveloppes issues d isolats primaires de primo-infection afin d identifier une enveloppe d intérêt comme immunogène bloquant l interaction avec le DC-SIGN. Nous avons ainsi pu identifier deux mutations dans la gp41 susceptibles d amplifier l interaction DC-SIGN /gp120. Enfin, nous avons étudié la capacité de prise en charge locale et spécifique d Aspergillus fumigatus par des extensions trans-épithéliales formées par les CD au niveau des villosités de l iléon terminal murin. Notre étude souligne le rôle primordial du DC-SIGN au niveau des muqueuses monostratifiées que ce soit pour la voie de contamination homosexuelle du VIH-1 ou pour l efficacité de capture de pathogènes par les dendrites trans-épithéliales des CDAs the sentinels of the immune system, DC express a lectin DC-SIGN known to bind with high affinity a wide range of pathogens, including HIV-1. The first aim of this study is to use this lectin as a screening tool for envelopes from acute HIV-1 primary isolates in order to identify an envelope of interest that could be used as an immunogen to block the interaction with DC-SIGN. We have identified two point mutations in the gp41 susceptible to increase the DC-SIGN/gp120 interaction. At last, we have studied the local and specific uptake of Aspergillus fumigatus by trans-epithelial dendrites formed by DC in villi of the murine terminal ileum. Our study highlights the crucial role of DC-SIGN in monolayered mucosa, as suggested by the predominance of HIV-1 homosexual contamination or the efficiency of DC trans-epithelial dendrites to capture pathogensLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Premalignant and pre-invasive lesions of the breast

Premalignant and pre-invasive lesions of the breast belong to a complex and heterogeneous group of lesions and represent a matter of remarkable interest from both clinical and biological standpoints. These frequent noninvasive alterations are related with an increased probability of breast cancer development. What is more, these breast abnormalities show extremely variable risks of progression toward invasive forms of disease. Indeed, while there are many histologically defined premalignant lesions in the breast, only a subset of them constitute true neoplastic precursors that will progress to invasive cancer. Disappointingly, it is currently not conceivable to identify a priori, with absolute certainty, which of these precursors will progress and which not. Therefore, classifying risk indicators, precursors, and non-obligate precursors of invasive breast cancer, and ultimately define robust protocols for their clinical management, is a hot topic in the multidisciplinary approach to breast cancer patients, that involves pathologists, radiologists, surgeons, and oncologists