Reference Detail

Ref Type

PMID

(36053791)

Authors

Hescot S, Masliah-Planchon J, du Rusquec P, Dupain C, Kamal M, Servois V, Bieche I

Title

Significant response to pralsetinib in a medullary thyroid cancer harboring double RET variants of unknown significance.

Journal	Vol	Issue	Date	Pages	Journal Short Title
European thyroid journal			2022 Sep 01		Eur Thyroid J

URL

Abstract Text

Medullary thyroid carcinoma (MTC) is a rare but aggressive thyroid tumor, with 25% of hereditary and 75% of sporadic forms. RET mutations are found in 98% of hereditary MTC and in 55% of sporadic MTC. The most frequent somatic RET mutation occurs in codon M918, reported in up to 90% of RET-positive MTC cases. Selpercatinib and pralsetinib, tyrosine-kinase inhibitors with a high specificity for RET protein, recently obtained FDA approval for the treatment of Lung and Thyroid Cancers with RET gene mutations or fusions. In MTC patients, phase I/II studies with RET inhibitors reported overall response rates of 73% and phase III are ongoing. Here we describe the case of a patient with metastatic MTC who harbored two somatic variants of unknown significance (VUS) in the RET gene and responded to Pralsetinib.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
RET	L1016S	missense	unknown	RET L1016S lies within the protein kinase domain of the Ret protein (UniProt.org). L1016S has been identified in the scientific literature (PMID: 36053791), but has not been biochemically characterized and therefore, its effect on Ret protein function is unknown (PubMed, Apr 2024).
RET	V591_G607del	deletion	unknown	RET V591_G607del results in the deletion of 17 amino acids in the extracellular domain of the Ret protein from amino acids 591 to 607 (UniProt.org). V591_G607del has been identified in the scientific literature (PMID: 36053791), but has not been biochemically characterized and therefore, its effect on Ret protein function is unknown (PubMed, Apr 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
RET V591_G607del RET L1016S	thyroid gland medullary carcinoma	predicted - sensitive	Pralsetinib	Case Reports/Case Series	Actionable	In a clinical case study, Gavreto (pralsetinib) treatment resulted in a partial response lasting more than 1 year in a patient with medullary thyroid carcinoma harboring RET V591_G607del and germline RET L1016S (PMID: 36053791).	36053791