Williamson Laura M, Steel Michael, Grewal Jasleen K, Thibodeau My Lihn, Zhao Eric Y, Loree Jonathan M, Yang Kevin C, Gorski Sharon M, Mungall Andrew J, Mungall Karen L, Moore Richard A, Marra Marco A, Laskin Janessa, Renouf Daniel J, Schaeffer David F, Jones Steven J M
Canada's Michael Smith Genome Science Centre, BC Cancer, Vancouver, British Columbia V5Z 4S6, Canada.
Department of Pathology & Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia V6T 2B5, Canada.
Cold Spring Harb Mol Case Stud. 2019 Jun 3;5(3). doi: 10.1101/mcs.a003814. Print 2019 Jun.
Pancreatic neuroendocrine neoplasms (PanNENs) represent a minority of pancreatic neoplasms that exhibit variability in prognosis. Ongoing mutational analyses of PanNENs have found recurrent abnormalities in chromatin remodeling genes (e.g., and ), and mTOR pathway genes (e.g., , , and ), some of which have relevance to patients with related familial syndromes. Most recently, grade 3 PanNENs have been divided into two groups based on differentiation, creating a new group of well-differentiated grade 3 neuroendocrine tumors (PanNETs) that have had a limited whole-genome level characterization to date. In a patient with a metastatic well-differentiated grade 3 PanNET, our study utilized whole-genome sequencing of liver metastases for the comparative analysis and detection of single-nucleotide variants, insertions and deletions, structural variants, and copy-number variants, with their biologic relevance confirmed by RNA sequencing. We found that this tumor most notably exhibited a -disrupting fusion, showed a novel fusion, and lacked any somatic variants in , , and .
胰腺神经内分泌肿瘤（PanNENs）占胰腺肿瘤的少数，其预后存在差异。对PanNENs进行的持续突变分析发现，染色质重塑基因（如……和……）以及mTOR通路基因（如……、……和……）存在反复出现的异常，其中一些与相关家族综合征患者有关。最近，3级PanNENs根据分化情况被分为两组，形成了一组新的高分化3级神经内分泌肿瘤（PanNETs），迄今为止，这组肿瘤在全基因组水平上的特征有限。在一名转移性高分化3级PanNET患者中，我们的研究利用肝转移灶的全基因组测序进行比较分析，并检测单核苷酸变异、插入和缺失、结构变异以及拷贝数变异，通过RNA测序证实了它们的生物学相关性。我们发现，该肿瘤最显著的表现是一个……破坏融合，显示出一种新的……融合，并且在……、……和……中没有任何体细胞变异。
