DNA 甲基化揭示了胰腺神经内分泌癌和胰腺神经内分泌肿瘤的不同起源细胞。
DNA methylation reveals distinct cells of origin for pancreatic neuroendocrine carcinomas and pancreatic neuroendocrine tumors.
机构信息
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hepatology and Gastroenterology, Berlin, Germany.
出版信息
Genome Med. 2022 Mar 1;14(1):24. doi: 10.1186/s13073-022-01018-w.
BACKGROUND
Pancreatic neuroendocrine neoplasms (PanNENs) fall into two subclasses: the well-differentiated, low- to high-grade pancreatic neuroendocrine tumors (PanNETs), and the poorly-differentiated, high-grade pancreatic neuroendocrine carcinomas (PanNECs). While recent studies suggest an endocrine descent of PanNETs, the origin of PanNECs remains unknown.
METHODS
We performed DNA methylation analysis for 57 PanNEN samples and found that distinct methylation profiles separated PanNENs into two major groups, clearly distinguishing high-grade PanNECs from other PanNETs including high-grade NETG3. DNA alterations and immunohistochemistry of cell-type markers PDX1, ARX, and SOX9 were utilized to further characterize PanNECs and their cell of origin in the pancreas.
RESULTS
Phylo-epigenetic and cell-type signature features derived from alpha, beta, acinar, and ductal adult cells suggest an exocrine cell of origin for PanNECs, thus separating them in cell lineage from other PanNENs of endocrine origin.
CONCLUSIONS
Our study provides a robust and clinically applicable method to clearly distinguish PanNECs from G3 PanNETs, improving patient stratification.
背景
胰腺神经内分泌肿瘤（PanNENs）分为两类：分化良好的低-高级别胰腺神经内分泌肿瘤（PanNETs）和分化差的高级别胰腺神经内分泌癌（PanNECs）。虽然最近的研究表明 PanNETs 来源于内分泌细胞，但 PanNECs 的起源仍不清楚。
方法
我们对 57 个 PanNEN 样本进行了 DNA 甲基化分析，发现不同的甲基化谱将 PanNENs 分为两个主要组，清楚地区分了高级别 PanNECs 和其他 PanNETs，包括高级别 NETG3。利用 DNA 改变和细胞类型标志物 PDX1、ARX 和 SOX9 的免疫组化进一步表征 PanNECs 及其在胰腺中的起源细胞。
结果
来自 alpha、beta、腺泡和导管成体细胞的系统发生和细胞类型特征提示 PanNECs 的起源于外分泌细胞，因此与其他起源于内分泌细胞的 PanNETs 在细胞谱系上分离。
结论
我们的研究提供了一种强大且临床适用的方法，可清楚地区分 PanNECs 和 G3 PanNETs，从而改善患者分层。
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