Making Sense of Missense: Assessing and Incorporating the Functional Impact of Constitutional Genetic Testing

Area of Science:

• Genetics
• Oncology
• Psychosocial Medicine

Background:

• Advancements in next-generation sequencing enable comprehensive genetic testing for pediatric cancers.
• Pediatric oncologists face increasing responsibility to identify cancer predisposition syndromes.
• Li-Fraumeni syndrome is a key hereditary cancer predisposition syndrome linked to TP53 gene mutations.

Purpose of the Study:

• To explore psychosocial themes associated with genetic testing for Li-Fraumeni syndrome.
• To integrate patient, parent, and healthcare provider perspectives in cancer predisposition syndrome testing.
• To identify opportunities for applying social themes to the biological understanding of TP53.

Main Methods:

• Triangulated interviews with family members diagnosed with Li-Fraumeni syndrome.
• Qualitative content analysis of interview data using NVivo 10.0 software.
• Thematic coding to identify psychosocial themes relevant to genetic testing, diagnosis, and surveillance.

Main Results:

• Interview data revealed significant psychosocial themes pertinent to the Li-Fraumeni syndrome diagnosis.
• Social themes emerged that parallel the biological language associated with TP53 gene function.
• The study identified key areas for improving the integration of diverse perspectives in genetic testing.

Conclusions:

• A model is proposed for systematically including patient, parent, and healthcare provider viewpoints.
• This approach enhances the understanding and management of familial cancer predisposition syndromes.
• Integrating psychosocial insights can improve the application of genetic testing in pediatric oncology.