Benefits for children with suspected cancer from routine whole-genome sequencing.

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.

Clinical, social and ethical issues associated with non-invasive prenatal testing for aneuploidy.

Non-invasive prenatal testing (NIPT), based on analysis of cell-free foetal DNA, is rapidly becoming a preferred method to screen for chromosomal aneuploidy with the technology now available in over 90 countries. This review provides an up-to-date discussion of the key clinical, social and ethical implications associated with this revolutionary technology. Stakeholders are positive about a test that is highly accurate, safe, can be perfomed early in pregnancy, identifies affected pregnancies that might otherwise have been missed and reduces the need for invasive testing. Nevertheless, professional societies currently recommend it as an advanced screening test due to the low false positive rate (FPR). Despite the practical and psychological benefits, a number of concerns have been raised which warrant attention. These include the potential for routinisation of testing and subsequent impact on informed decision-making, an "easy" blood test inadvertently contributing to women feeling pressured to take the test, fears NIPT will lead to less tolerance and support for those living with Down syndrome and the heightened expectation of having "perfect babies". These issues can be addressed to some extent through clinician education, patient information and establishing national and international consensus in the development of comprehensive and regularly updated guidelines. As the number of conditions we are able to test for non-invasively expands it will be increasingly important to ensure pre-test counselling can be delivered effectively supported by knowledgeable healthcare professionals.