Genomic testing for RET in the clinic: UK and global perspective
Abstract:
RET is a key oncogene in neuroendocrine cancer. Pathogenic germline variants lead to multiple different phenotypes, including multiple endocrine neoplasia type 2, 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 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, as well as 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. Finally, 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.
Insights
RET gene testing is crucial for diagnosing neuroendocrine cancers and related conditions. Identifying RET variants guides personalized cancer treatment and family screening, improving patient outcomes.
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.
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