Genomic testing for RET in the clinic: UK and global perspective

Area of Science:

• Oncology
• Genetics
• Genomics

Background:

• RET is a key oncogene implicated in neuroendocrine cancers.
• Pathogenic germline and somatic variants in RET are linked to various phenotypes, including medullary thyroid cancer (MTC), Hirschsprung disease, and kidney malformations.
• RET rearrangements are found in papillary thyroid cancer, non-small cell lung cancer, and pan-cancer syndromes.

Purpose of the Study:

• To review current germline and somatic RET variant testing strategies globally.
• To discuss the clinical implications of identifying RET variants, including personalized cancer treatment and family implications.
• To explore challenges in providing rapid and equitable access to genomic testing for RET variants.

Main Methods:

• Review of current germline and somatic testing strategies.
• Discussion of reporting and test outcomes, including variants of uncertain significance and incidental findings.
• Exploration of actions following identification of pathogenic germline variants and somatic RET variants in solid tumors.

Main Results:

• Germline and somatic RET variant testing is feasible in clinical practice.
• Identification of RET variants has significant clinical consequences for individuals and families.
• RET variant testing informs personalized cancer treatment and predictive/reproductive/childhood testing.

Conclusions:

• Effective RET variant testing strategies are essential for improved clinical outcomes.
• Equitable and timely access to genomic testing is critical for all patients.
• Understanding RET variant implications aids in personalized medicine and family health management.