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

Abstract

RET is a key oncogene in neuro-endocrine cancer. Pathogenic germline variants lead to multiple different phenotypes, including multiple endocrine neoplasia type 2 (MEN2), medullary thyroid cancer (MTC), Hirschsprung disease, and kidney malformations. Pathogenic somatic variants are also associated with MTC; and RET rearrangements are observed in papillary thyroid cancer, non-small cell lung cancer (NSCLC) and pan-cancer syndromes. Testing for both germline and somatic variants is now feasible in everyday clinical practice; and their identification has important clinical consequences, both for affected individuals and their families. This mini review will discuss current germline and somatic testing strategies in the UK and worldwide, reporting, and test outcomes (including variants of uncertain significance or incidental findings). It will explore actions following identification of a pathogenic germline variant, including predictive, reproductive, and childhood testing; and somatic testing of RET variants in solid tumours informing personalised cancer treatment. Lastly, it will discuss the challenge of delivering rapid and equitable access to genomic testing, to ensure that all individuals can benefit promptly and appropriately, to improve clinical outcomes.