Ethical considerations surrounding germline next-generation sequencing of children with cancer

Abstract

The advent of next-generation sequencing (NGS) has introduced an exciting new era in biomedical research. NGS forms the foundation of current genetic testing approaches, including targeted gene panel testing, as well as more comprehensive whole-exome and whole-genome sequencing. Together, these approaches promise to provide critical insights into the understanding of health and disease. However, with NGS testing come many ethical questions and concerns, particularly when testing involves children. These concerns are especially relevant for children with cancer, where the testing of tumor and germline tissues is increasingly being incorporated into clinical care. Areas covered: In this manuscript, we explore the key ethical considerations related to conducting germline NGS testing in pediatric oncology, focusing on the four main principles of beneficence, non-maleficence, autonomy and justice. Expert commentary: The ethical issues surrounding germline NGS testing are complex and result in part from our limited understanding of the medical relevance of many of the results obtained and poor knowledge of the impacts of testing, both beneficial and detrimental, on patients and their families. In this article we discuss the risks and benefits of germline NGS testing and the arguments for and against such testing in children with cancer.

Speaking genomics to parents offered germline testing for cancer predisposition: Use of a 2‐visit consent model

“…Predictive genomic sequencing is increasingly common in oncology but is not without ethical concerns in the context of pediatrics . It is critical that clinicians communicate effectively with parents to delineate the differences between somatic and germline testing and the implications thereof.…”

“…Predictive genomic sequencing is increasingly common in oncology but is not without ethical concerns in the context of pediatrics. 11 It is critical that clinicians communicate effectively with parents to delineate the differences between somatic and germline testing and the implications thereof. In other populations, individuals with low levels of genetic knowledge have difficulty in forming opinions about genomic testing when this knowledge is required to make a treatment-related decision.…”

“…However, germline sequencing is not without its potential risks, and many professional guidelines recommend against broadly testing children for heritable genetic conditions that have no actionability in childhood . For example, in addition to learning about an underlying cancer predisposition, families may receive information about the presence of a nononcologic disorder in their child, or they may receive results of uncertain clinical significance . Because a relatively small proportion of patients will receive information that is immediately actionable, there is an ethical imperative to perform quality informed consent conversations (ICCs) with patients and families about the risks and benefits of germline testing.…”

Parent–child communication surrounding genetic testing for Li–Fraumeni syndrome: Living under the cloud of cancer

“…Parents are the primary gatekeepers of medical knowledge and communication with their children . This is particularly challenging when children are perceived to be too young to understand the implications of testing or participate in decisions about testing . In this study, parents expressed a desire to hold conversations when they felt their children were “ready.” Deciding upon the appropriate developmental stage at which to disclose vital health information is often left to parents and wrought with uncertainty .…”

Pediatric cancer families’ participation in whole-genome sequencing research in Denmark: Parent perspectives

“…Although genomic sequencing is not currently routine in paediatric oncology, a few studies have recently introduced WGS and/or whole exome sequencing to families of newly diagnosed paediatric cancer patients, not least in anticipation of sequencing's transition from laboratory to clinic (Parsons et al, 2016;Zhang et al, 2015). Further to meaningful informed consent and decision-making, WGS research with newly diagnosed childhood cancer patients also raises a set of ethical and social challenges around potential long-term consequences arising from findings (primary or secondary), potential involvement of other family members, children's right to an open future, data security and privacy, the establishing of biobanks for future research and the potential implications of important future knowledge for patients who have donated DNA to a biobank (Johnson et al, 2017).…”