Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 107, Issue 8, Pages 2195-2202Publisher
ENDOCRINE SOC
DOI: 10.1210/clinem/dgac325
Keywords
medullary thyroid carcinoma; RET indels; NGS; next-generation sequencing; selpercatinib; tyrosine kinase inhibitor
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [21790]
- Agenzia Italiana del Farmaco (AIFA) [AIFA-2016-02365049]
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RET indels are not uncommon in MTC patients and are associated with aggressive disease. Two patients with RET indels showed partial response to treatment with Selpercatinib.
Context Although the majority of RET alterations are single nucleotide variants (SNV), small deletions and/or insertions have been reported at variable prevalence. No information about the efficacy of RET-specific inhibitors in patients harboring RET indels has been provided. Objective We present an update on the prevalence of RET indels in medullary thyroid cancer (MTC) and describe the efficacy of selpercatinib in patients with advanced MTC with RET indels. Methods The MTC tissues of 287 patients were analyzed using an Ion S5 targeted sequencing. The functional role of the reported indels have been evaluated by MutationTaster. Clinical and pathological data of MTC patients harboring a RET indel were collected and analyzed. Two patients with a RET indel were treated with selpercatinib. Results Among 178 RET-positive cases, 147 (82.6%) harbored a SNV and 31 (17.4%) a RET in-frame indel. Nine indels were not previously reported and were found to be disease causing by MutationTaster. Patients harboring an indel were found to have an aggressive disease and 2 of them were treated with selpercatinib, experiencing a good response to the treatment. Conclusion These data show that RET indels are not infrequent and correlate with an aggressive disease. Two RET indel-positive patients showed a partial response to the treatment with a highly selective RET inhibitor; thus, these RET indels can be considered actionable mutations. In order to not miss these alterations, the analysis of the full gene is recommended.
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