The Laboratory of Clinical Genetics, Medical Research Center.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Eur J Endocrinol. 2022 May 19;187(1):85-90. doi: 10.1530/EJE-21-0893.
The pancreatic neuroendocrine tumors (PanNETs) are a group of clinically heterogeneous neoplasms. Although previous studies illustrated the somatic mutation pattern for PanNETs, the germline mutation pattern is still unclear. Here, we comprehensively screened the underlying germline mutations in a cohort of multiple endocrine neoplasia type 1 (MEN1)-related and sporadic PanNETs to reveal the characteristics of germline mutation in PanNET patients.
Patients diagnosed with PanNETs by biopsy or surgical pathology were enrolled in this study. Peripheral blood samples were used for genomic DNA purification and subsequent sequencing. The following sequencing techniques were used and compared for validation: (1) targeted gene capture with a customized panel; (2) whole exome sequencing data from previous study.
A total of 184 PanNET patients were enrolled, including 20 MEN1-related and 164 sporadic cases. In this study, MEN1 mutation rate in MEN1-related PanNETs was 60% (12/20), of which 50% were novel mutation sites. For sporadic PanNETs, the overall germline mutation rate was very low. Besides the rare MEN1 mutation, previously unreported germline variant in DAXX was found in one non-functional PanNET.
This study revealed distinctive germline mutation rates between MEN1-related and sporadic PanNETs. The novel MEN1 mutations contribute to revealing the spectrum of MEN1 mutations in PanNETs. The newly discovered germline variant of DAXX in sporadic PanNET implies a tendency of convergence between germline and somatic mutation genes.
胰腺神经内分泌肿瘤（PanNETs）是一组临床异质性的肿瘤。虽然先前的研究阐明了 PanNETs 的体细胞突变模式，但种系突变模式仍不清楚。在这里，我们全面筛选了一组多发性内分泌肿瘤 1 型（MEN1）相关和散发性 PanNETs 的潜在种系突变，以揭示 PanNET 患者种系突变的特征。
通过活检或手术病理诊断为 PanNETs 的患者被纳入本研究。采集外周血样本用于基因组 DNA 纯化，随后进行测序。使用了以下测序技术并进行了比较验证：（1）使用定制面板进行靶向基因捕获；（2）来自先前研究的全外显子组测序数据。
共纳入 184 例 PanNET 患者，包括 20 例 MEN1 相关和 164 例散发性病例。在本研究中，MEN1 相关 PanNETs 中的 MEN1 突变率为 60%（12/20），其中 50%为新的突变位点。对于散发性 PanNETs，种系突变率非常低。除了罕见的 MEN1 突变外，还在一例无功能 PanNET 中发现了以前未报道的 DAXX 种系变异。
本研究揭示了 MEN1 相关和散发性 PanNETs 之间独特的种系突变率。新发现的 MEN1 突变有助于揭示 PanNETs 中 MEN1 突变的谱。在散发性 PanNETs 中发现的 DAXX 种系变异暗示了种系和体细胞突变基因之间的趋同倾向。
