散发性甲状腺髓样癌中的体细胞 RET 插入缺失：患病率和对塞尔帕替尼的反应。

Somatic RET Indels in Sporadic Medullary Thyroid Cancer: Prevalence and Response to Selpercatinib.

机构信息

Unit of Endocrinology, Department of Clinical and Experimental Medicine, University-Hospital of Pisa, 56124 Pisa, Italy.

Endocrine Dept., 401 General Military Hospital of Athens, Athens 11525, Greece.

出版信息

J Clin Endocrinol Metab. 2022 Jul 14;107(8):2195-2202. doi: 10.1210/clinem/dgac325.

DOI:10.1210/clinem/dgac325

PMID:35616103

Abstract

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.

摘要

背景

虽然大多数 RET 改变是单核苷酸变异（SNV），但已报道在不同的流行率下存在小的缺失和/或插入。尚未提供关于 RET 特异性抑制剂在携带 RET 插入缺失的患者中的疗效信息。

目的

我们报告了甲状腺髓样癌（MTC）中 RET 插入缺失的流行率更新，并描述了在携带 RET 插入缺失的晚期 MTC 患者中使用塞普替尼的疗效。

方法

使用 Ion S5 靶向测序分析了 287 例 MTC 组织。通过 MutationTaster 评估了报道的插入缺失的功能作用。收集和分析了携带 RET 插入缺失的 MTC 患者的临床和病理数据。对两名携带 RET 插入缺失的患者进行了塞普替尼治疗。

结果

在 178 例 RET 阳性病例中，147 例（82.6%）携带 SNV，31 例（17.4%）携带 RET 框内插入缺失。有 9 个插入缺失以前没有报道过，通过 MutationTaster 发现它们是致病的。携带插入缺失的患者被发现患有侵袭性疾病，其中 2 名患者接受了塞普替尼治疗，对治疗有良好的反应。