Au-delà de la technologie : travailler à la fiabilité de la prédiction génétique

International audienceLa prédiction est une dimension importante des usages cliniques de la génétique. Ses capacités en la matière sont fréquemment surestimées, dans certains discours relevant d'un régime de promesses technoscientifiques. En considérant successivement la génétique des maladies rares et l'oncogénétique, dans lesquelles la prédiction génétique est pratiquée de longue date, nous soutenons que l'image des technologies génomiques comme productrices de prédictions fiables n'est pas uniquement la conséquence de ces promesses technoscientifiques et commerciales. Elle résulte également d'un travail important de la part des professionnels, constant mais peu visible, pour réguler les usages de la prédiction génétique. Ledit travail a pour conséquence de minimiser l'incertitude perceptible par les cercles extérieurs. Dans un contexte de forte pression (notamment commerciale) à l'extension des usages des tests, une telle situation pose d'importantes questions politiques

Genomic Platforms at Work: a French Case Study

International audienceDeveloping and applying cancer genomics in both research and healthcare has been a French national priority for more than ten years. In 2006, following the first authorization to market a targeted therapy conditioned on a genetic test, and a competitive call for proposals, the French National Cancer Institute (INCa) and the French Ministry of Health set up a national network of 28 approved regional molecular genetics platforms (Nowak et al, 2012). These platforms are funded annually to perform the molecular tests needed to deliver targeted therapies to all patients in their respective regions, regardless of the institution where they are treated. Although these platforms all respect the quality insurance and organizational guidelines drafted by INCa, they vary in their institutional trajectory, size and modes of organization.To better understand how genomic platforms function on a daily basis, we conducted a collective exploratory ethnographic study of one of these regional platforms, located in a public university hospital of the Auvergne‐Rhône‐Alpes region (CHU de Grenoble). Based in a general hospital that is not a comprehensive cancer centre, this platform provides a relevant site for observing and analysing the organizational, professional and epistemic issues that are raised by the routinization of oncogenomics.In this presentation, we describe and analyse the trajectory of a solid tumour biopsy from its entry into the platform to the writing of the molecular report sent to prescribing clinicians. Our analysis focuses on key moments in the course of this trajectory. We highlight the ways in which the platform brings together social worlds with little previous collaborative experiences. We describe the negotiations and efforts to coordinate the work of different sites and forms of expertise in a context where novel genomic technologies must be “domesticated”. We show how local context and history influence the solutions adopted and report the importance of tinkering practices. Interestingly, strategies to manage varying degrees of personal engagement appear to be central to the success of this collective implementation of personalized medicine

Genomic Platforms at Work: a French Case Study

International audienceDeveloping and applying cancer genomics in both research and healthcare has been a French national priority for more than ten years. In 2006, following the first authorization to market a targeted therapy conditioned on a genetic test, and a competitive call for proposals, the French National Cancer Institute (INCa) and the French Ministry of Health set up a national network of 28 approved regional molecular genetics platforms (Nowak et al, 2012). These platforms are funded annually to perform the molecular tests needed to deliver targeted therapies to all patients in their respective regions, regardless of the institution where they are treated. Although these platforms all respect the quality insurance and organizational guidelines drafted by INCa, they vary in their institutional trajectory, size and modes of organization.To better understand how genomic platforms function on a daily basis, we conducted a collective exploratory ethnographic study of one of these regional platforms, located in a public university hospital of the Auvergne‐Rhône‐Alpes region (CHU de Grenoble). Based in a general hospital that is not a comprehensive cancer centre, this platform provides a relevant site for observing and analysing the organizational, professional and epistemic issues that are raised by the routinization of oncogenomics.In this presentation, we describe and analyse the trajectory of a solid tumour biopsy from its entry into the platform to the writing of the molecular report sent to prescribing clinicians. Our analysis focuses on key moments in the course of this trajectory. We highlight the ways in which the platform brings together social worlds with little previous collaborative experiences. We describe the negotiations and efforts to coordinate the work of different sites and forms of expertise in a context where novel genomic technologies must be “domesticated”. We show how local context and history influence the solutions adopted and report the importance of tinkering practices. Interestingly, strategies to manage varying degrees of personal engagement appear to be central to the success of this collective implementation of personalized medicine

Improved detection of DNA aneuploidy in primary breast cancer using quantitative DNA image analysis in combination with fluorescent in situ hybridization technique

To obtain more information about the relationship between numerical aberrations of chromosome 1 and the overall DNA content of breast cancer cells, fluorescent in situ hybridization with a pericentromeric probe for this chromosome and image analysis based densitometry were carried out on imprints of benign (15 cases, mainly fibroadenomas) and malignant breast disease (31 invasive ductal carcinomas out of 45 cases). The most pronounced aneuploidy was observed in invasive ductal and lobular carcinoma cases both by in situ hybridization and DNA content (76.7 and 75.0% were aneuploid). The frequency of cells with two spots for chromosome 1 was 48.3 and 51.5%, respectively, as compared to 80.3% in control lymphocytes. There was a weak overall correlation (r2 = 0.83) between DNA content and copy number of chromosome 1 in the malignant samples, although some of the DNA diploid/near diploid carcinomas showed a marked aneusomy for this chromosome. Also, some aberrations were present in the benign breast disease samples. Classification of cases by a linear discriminant analysis was most accurate when both techniques were combined (77% of cases correctly classified, according to anatomo-pathological diagnosis). The variables which received the highest weight in the linear discriminant function are the percentage DNA-diploid cells and the fraction of cells with two spots for chromosome 1. The sensitivity and sources of error of both techniques is considered. © 1995 Chapman & Hall.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Aneuploidy for chromosome 1 and overall DNA content in benign and malignant breast disease

Fluorescence in situ hybridization (FISH) with a probe for the pericentromeric region of chromosome 1 and DNA content measurements by image-analysis-based densitometry have been carried out on imprints of benign and malignant breast tissue. In general, an increase in the number of spots per nucleus was observed in the invasive carcinomas, with a large intercellular variation. In comparison with lymphocytes from controls, some cases of benign breast disease already had an increased frequency of aneusomy of chromosome 1, although they were all (near)diploid by DNA-content. However, an overall concordance between the DNA content measurements and the results of FISH was observed, although some exceptions were seen. A statistically significant correlation between the DNA index and the mean number of spots for chromosome 1 per nucleus was found. A linear discriminant analysis was applied on the data; the resulting classification of patients was most accurate when parameters describing DNA content and FISH results were combined. © 1994.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cytokeratin expression by CD34 positive blasts in a case of refractory anaemia with excess of blasts in transformation (RAEB-t) [3]

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Breast imaging. Preoperative breast cancer staging: Comparison of USPIO-enhanced MR imaging and 18F-fluorodeoxyglucose (FDC) positron emission tomography (PET) imaging for axillary lymph node staging - Initial findings

Magnetic resonance (MR) imaging after ultra-small super paramagnetic iron oxide (USPIO) injection and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperative axillary lymph node staging in patients with breast cancer were evaluated using histopathologic findings as the reference standard. USPIO-enhanced MR and FDG-PET were performed in ten patients with breast cancer who were scheduled for surgery and axillary node resection. T2-weighted fast spin echo, T1-weighted three-dimensional (3D) gradient echo, T2*-weighted gradient echo and gadolinium-enhanced T1-weighted 3D gradient echo with spectral fat saturation were evaluated. MR imaging before USPIO infusion was not performed. The results were correlated with FDG-PET (acquired with dedicated PET camera, visual analysis) and histological findings. The histopathologic axillary staging was negative for nodal malignancy in five patients and positive in the remaining five patients. There was one false positive finding for USPIO-enhanced MR and one false negative finding for FDG-PET. A sensitivity (true positive rate) of 100%, specificity (true negative rate) of 80%, positive predictive value of 80%, and negative predictive value of 100% were achieved for USPIO-enhanced MR and of 80%, 100%, 100%, 80% for FDG-PET, respectively. The most useful sequences in the detection of invaded lymph nodes were in the decreasing order: gadolinium-enhanced T1-weighted 3D gradient echo with fat saturation, T2*-weighted 2D gradient echo, T1-weighted 3D gradient echo and T2-weighted 2D spin echo. In our study, USPIO-enhanced T1 gradient echo after gadolinium injection and fat saturation emerged as a very useful sequence in the staging of lymph nodes. The combination of USPIO-enhanced MR and FDG-PET achieved 100% sensitivity, specificity, PPV and NPV. If these results are confirmed, the combination of USPIO MR with FDG-PET has the potential to identify the patient candidates for axillary dissection versus sentinel node lymphadenectomy. © Springer-Verlag 2006.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

In vitro fertilization pregnancy in a patient with proven chronic endometritis

Objective: To report an in vitro fertilization (IVF) pregnancy in a patient with histologically confirmed chronic endometritis before the IVF treatment without prior antibiotherapy. Design: Case report. Setting: Academic reproductive medicine unit. Patient(s): A30-year-oldwoman with primary infertility due to mild oligoasthenoteratospermia of the male partner. Intervention(s): Diagnostic hysteroscopy and endometrial biopsy. Main Outcome Measure(s): Delivery after the first IVF. Result(s): Histologic examination of the endometrium revealed chronic endometritis. The patient delivered a healthy boy at 40 weeks' gestation after the first IVF treatment. Conclusion(s): Our findings suggest that the impact of chronic endometritis on infertility and IVF outcome should be further investigated in prospective randomized studies. (Fertil Steril (R) 2009;91:1293.e9-e11. (C) 2009 by American Society for Reproductive Medicine.