Managing expectations, rights, and duties in large-scale genomics initiatives: a European comparison

This article reports on the findings of an international workshop organised by the UK-France Genomics and Ethics Network (UK-FR GENE) in 2021. They focus specifically on how collection, storage and sharing of genomic data may pose challenges to established principles and values such as trust, confidentiality, and privacy in countries that have implemented, or are about to implement, large-scale national genomic initiatives. These challenges impact the relationships between patients/citizens and medicine/science, and on each party’s rights and duties towards each other. Our geographic scope of comparative analysis includes initiatives underway in England (Genomics England), France (Plan France Médecine Génomique) and Germany (German Human Genome-Phenome Archive). We discuss existing as well as future challenges raised by large-scale health data collection and management in each country. We conclude that the prospects of improving individualised patient healthcare as well as contributing to the scientific and research prosperity of any given nation engaged in health data collection, storage and processing are undeniable. However, we also attempt to demonstrate that biomedical data requires careful management, and transparent and accountable governance structures that are clearly communicated to patients/participants and citizens. Furthermore, when third parties partake as stakeholders, transparent consent protocols relative to data access and use come centre stage, and patient benefits must clearly outweigh commercial interests. Finally, any cross-border data transfer needs to be carefully managed to address incoherencies between regional, national, and supranational regulations and recommendations

Fostering responsible research with genome editing technologies : a European perspective

In this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation.peer-reviewe

Artificial Wombs: The Third Era of Human Reproduction and the Likely Impact on French and U.S. Law

Advances in reproductive technology are outpacing statutory and regulatory authority, and artificial wombs as a form of assistive reproductive technology are no longer the subject of science fiction. This article begins with insight to the original ideas of artificial wombs and the subsequent effect these ideas had science and technology at the time. Artificial wombs, being disconnected from the body, were the subjects of dystopian portrayals of society, and many critics denied the possibility that such technology would ever exist. Experiments in the 20th century, however, have made artificial wombs a real possibility. The author explores how artificial wombs would fit within various legal frameworks in France and the U.S., and suggests incorporating surrogacy laws into artificial womb regulation

A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in <i>HER2</i>-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways

<div><p>Introduction</p><p><i>HER2</i>-positive breast cancer (BC) is a heterogeneous group of aggressive breast cancers, the prognosis of which has greatly improved since the introduction of treatments targeting <i>HER2</i>. However, these tumors may display intrinsic or acquired resistance to treatment, and classifiers of <i>HER2</i>-positive tumors are required to improve the prediction of prognosis and to develop novel therapeutic interventions.</p><p>Methods</p><p>We analyzed 2893 primary human breast cancer samples from 21 publicly available datasets and developed a six-metagene signature on a training set of 448 <i>HER2</i>-positive BC. We then used external public datasets to assess the ability of these metagenes to predict the response to chemotherapy (Ignatiadis dataset), and prognosis (METABRIC dataset).</p><p>Results</p><p>We identified a six-metagene signature (138 genes) containing metagenes enriched in different gene ontologies. The gene clusters were named as follows: Immunity, Tumor suppressors/proliferation, Interferon, Signal transduction, Hormone/survival and Matrix clusters. In all datasets, the Immunity metagene was less strongly expressed in ER-positive than in ER-negative tumors, and was inversely correlated with the Hormonal/survival metagene. Within the signature, multivariate analyses showed that strong expression of the “Immunity” metagene was associated with higher pCR rates after NAC (OR = 3.71[1.28–11.91], <i>p</i> = 0.019) than weak expression, and with a better prognosis in <i>HER2</i>-positive/ER-negative breast cancers (HR = 0.58 [0.36–0.94], <i>p</i> = 0.026). Immunity metagene expression was associated with the presence of tumor-infiltrating lymphocytes (TILs).</p><p>Conclusion</p><p>The identification of a predictive and prognostic immune module in <i>HER2</i>-positive BC confirms the need for clinical testing for immune checkpoint modulators and vaccines for this specific subtype. The inverse correlation between Immunity and hormone pathways opens research perspectives and deserves further investigation.</p></div

Lymphocytic infiltration in breast tumors.

<p><b>A</b> and <b>B:</b> Tumor specimen with weak lymphocytic infiltration (A: zoom x10 B: zoom x 40). Abbreviations: S = stroma, T = tumor, L = lymphocytes. Intratumoral TILs are indicated by a black star. <b>C</b> and <b>D</b>: Tumor specimen with prominent lymphocytic infiltration. (C: zoom x10 D: zoom x 40). Abbreviations: S = stroma, T = tumor, L = lymphocytes. Intratumoral TILs are indicated by a black star; stromal TILs are indicated by a blue star.</p

Association between tumor-infiltrating lymphocyte levels and Immunity metagene expression in the REMAGUS dataset.

<p><b>A:</b> Percentage of intratumoral TILs according to Immunity metagene status (low <i>versus</i> high). <b>B</b> Percentage of stromal TILs according to Immunity metagene status (low <i>versus</i> high). <b>C</b>: Correlation between metagene expression and the percentages of intratumoral TILs. <b>D</b>: Correlation between metagene expression and the percentage of stromal TILs.</p

pCR and DSS outcomes in the Ignatiadis and the METABRIC dataset.

<p><b>A:</b> pCR rates by ER and Immunity metagene status (low <i>versus</i> high in the Ignatiadis dataset). <b>B:</b> Kaplan-Meier plots. Disease-specific survival of the ER-negative population (<i>n</i> = 138) according to Immunity metagene expression (low/high) and nodal status in the METABRIC dataset.</p

Survival analysis (disease-specific survival) in the METABRIC dataset (univariate and multivariate analysis); whole population and ER-negative population.

<p>Survival analysis (disease-specific survival) in the METABRIC dataset (univariate and multivariate analysis); whole population and ER-negative population.</p