PDF(Pubmed)
Abstract：
This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.
摘要：
本研究的目的是确定染色体作为一种新的生物标志物在胰腺神经内分泌肿瘤（pNENs）的预后和鉴别诊断中的作用。我们在30例高级别（G3）pNENs患者的队列中进行了下一代基因测序。作为参考,对25例低级别(G1/G2)胰腺神经内分泌肿瘤(pNETs)患者也进行了类似的分析.本研究探讨了嗜铬细胞增多症及其与临床病理特征和预后的关系。结果显示，29例和11例患者中发现DNA损伤反应和修复基因改变以及TP53突变，分别。55例患者中，共有14例出现涉及不同染色体的染色体增生。嗜铬细胞增多症与TP53改变和较高等级有密切关系。在整个队列中，色素沉着与较高的远处转移风险相关；色素沉着和转移（ENETSIV期）均表明总生存期（OS）明显较短。重要的是,在高级pNENs组中，嗜血杆菌是唯一与较短OS显著相关的独立预后指标，除TP53改变或病理性胰腺神经内分泌癌（pNECs）诊断外。嗜铬细胞增多症可以指导pNENs预后较差，并帮助区分pNEC和高级（G3）pNETs。
