Opportunistic genomic screening: Ethical exploration

Diagnostic testing based on next-generation sequencing (NGS) is increasingly used in patient care to clarify the cause of complex disorders. Given the falling price of sequencing technology it is expected that in the near future most patients with an indication for genetic testing will have their exomes or genomes sequenced. This has led to debate about whether the analysis of raw NGS data thus obtained should be targeted to the clinical indication at hand or widened to include mutations or risk factors for other (clinically relevant) conditions beyond that indication. Like individual experts, professional bodies have different views. The European Society of Human Genetics (ESHG) has insisted that genomic analysis should be as targeted as possible, at least for the time being. However, the American College of Medical Genetics and Genomics (ACMG) recommends to routinely analyze a series of “actionable mutations” in each case of clinical sequencing, a strategy termed “opportunistic genomic screening” (OGS). While this proposal has led to considerable debate in the United States, a truly European discussion still needs to be started. Most recently, just before the submission of the current ethical reflection, the French Society of Predictive and Personalized Medicine (SFMPP) published its guidelines on “reporting secondary findings of genome sequencing in cancer genes.” The current reflection aims to stimulate a wider normative debate on OGS. Is OGS to be regarded as ethically (and legally) acceptable or even recommendable, and if so, on which conditions? We use the ACMG Recommendations as a frame of reference for further debate and ethical reflection, but will occasionally refer also to the SFMPP’s proposal. This ethical reflection is to a large extent explorative, aimed at identifying central ethical issues for further debate and analysis, thereby contributing to moral agenda-setting.