Feasibility Study of Opportunistic Genomic Screening in Pediatric Cancer Patients and Its Family Acceptance

Research Background
With the development and application of genomic medicine, the care for patients with severe diseases is gradually being optimized. Especially in the field of childhood cancer, whole-genome series DNA testing has become an important means of patient management. A follow-up work focusing on mosaic research examined the medical impact of opportunistic genomic screening (OGS) in this patient group and their relatives. The study quantified the actionability and acceptance of cascade testing over time after the disclosure of OGS results. The study pointed out that secondary findings were reported in ¹⁹⁄₅₉₅ (3.2%) of patients, mainly related to genes associated with cardiovascular and lipid disorders.

Research Source
This research team consists of multiple experts including Sophia Hammer-Hansen 1, Ulrik Stoltze 1,2, Emil Bartels 3,4, etc., representing various departments of Rigshospitalet, Copenhagen University Hospital in Denmark. The study was published in the “European Journal of Human Genetics” in 2024, available online through DOI 10.1038/s41431-024-01618-7.

Research Details
a) Research Process
This prospective multicenter genomic sequencing study, named STAGING, included children under 18 years of age diagnosed with any cancer or central nervous system tumor from January 1, 2017. Patients received in-depth genetic counseling and guidance from relevant experts after receiving feasible actionable gene findings. VarSeq (Golden Helix) was used for variant annotation and filtering. All variants considered coding, splice variants, and variant allele scores. Additionally, variants were evaluated according to ACMG guidelines, with detailed methods described in the supplementary methods.

b) Main Results
Among the 19 secondary findings, 7 were classified as PV (Pathogenic Variant) and 12 as LPV (Likely Pathogenic Variant). The involved genes and diseases include LDLR and APOB (associated with lipid disorders), as well as DSG2 and MYBPC3 (associated with cardiomyopathy). In the follow-up treatment of patients and families, it was found that in most cases, regular follow-ups and medical treatment plans were carried out, but no invasive surgeries or medical device implantations were performed.

c) Research Conclusions and Significance
Opportunistic genomic screening is applicable to pediatric cancer patients and their families, and has a broad impact on family members. Conducting such screening can effectively assist in the diagnosis, treatment, and management of related diseases, but at the same time, attention needs to be paid to the correct interpretation of genetic variants and consideration of potential psychological impacts.

d) Research Highlights
This study reveals the practical application of opportunistic genomic screening in routine diagnosis and treatment and its impact on healthcare needs. It provides a new perspective on the practical innovations brought by genotype-first screening and the demand for healthcare.

This research demonstrates the potential of using opportunistic genomic screening to identify medically actionable potential in pediatric cancer patients, and the findings have significant clinical implications for both the patients themselves and their family members. By quantifying the actionability and acceptance of cascade testing, the study reinforces the applicability and benefits of genetic screening in clinical practice. Although this study has found positive applications in the pediatric cancer patient population, future research will further explore the broad genetic significance and psychological impact on family members through methods such as structured interviews.