Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2023) 94 RET1.2 | DOI: 10.1530/endoabs.94.RET1.2

SFEBES2023 RET@30 Symposium Sessions Section (7 abstracts)

Current understanding of RET genotype-phenotype correlation

Louise Izatt


Department of Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom. Department of Medical and Molecular Genetics, King’s College London, London, United Kingdom


The ret proto-oncogene (RET) encodes a transmembrane tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic family, essential for the normal development of the kidneys, ureters, peripheral and enteric nervous system. Pathogenic variants in the RET gene result in multiple different phenotypes, which can range from isolated pathologies to multi-system disease, as a result of both loss and gain of RET function. Missense gain of function pathogenic variants in the RET proto-oncogene cause Multiple Endocrine Neoplasia type 2 (MEN2), an autosomal dominant cancer syndrome, where the hallmark of disease is development of medullary thyroid cancer (MTC). There are distinct subtypes of MEN2:- MEN2A, which includes families formerly described as familial MTC (FMTC), MEN2A with cutaneous lichen amyloidosis, MEN2A and Hirschsprung disease (HD) and MEN2B. The aggressiveness of MTC is correlated with specific RET pathogenic variants and stratified into three risk levels (highest, high, and moderate risk) based on the penetrance and aggressiveness of the MTC. Families with MEN2A may develop phaeochromocytomas (PCC) and primary hyperparathyroidism. In MEN2B, MTC develops early, often predating striking physical features that develop (Marfanoid habitus, mucosal neuromas, coarse facies and ganglioneuromatosis) and PCC. Activating somatic RET mutations are linked to development of sporadic MTC. Gain of function RET gene rearrangements also cause a subset of papillary thyroid cancer, lung cancer and chronic myelomonocytic leukaemia cases. In contrast, loss of function pathogenic variants throughout the RET gene are identified in 50% of patients with hereditary HD and 15-20% of patients with sporadic HD. Furthermore, inactivating pathogenic RET variants are identified in 5-30% patients with Congenital anomalies of the kidneys or urinary tract and kidney agenesis. This talk will highlight how knowledge gained over the last 30 years can be used to personalise care in respect to inherited oncogenic driver pathogenic variants in MEN2.

Volume 94

Society for Endocrinology BES 2023

Glasgow, UK
13 Nov 2023 - 15 Nov 2023

Society for Endocrinology 

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