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增强子标记可对非功能性胰腺神经内分泌肿瘤进行分型
来源:小柯机器人 发布时间:2019/8/12 14:46:55

美国波士顿丹娜法伯癌症研究院Ramesh A. Shivdasani课题组近日取得一项新成果。他们研究发现增强子标记能够对非功能性胰腺神经内分泌肿瘤进行分型并进行结果预测。 这一研究成果发表在2019年8月出版的国际学术期刊《自然—医学》上。

该课题组研究人员利用增强子图谱推断基因调控程序,发现非功能性PNET分为两个主要亚型,胰岛α和β细胞。转录因子ARX和PDX1分别专一性调控这些正常细胞,142个非功能性PNET中84%表达一个或另一个转录因子,偶尔两者都表达。在103例患者中,复发几乎只存在于表达ARX + PDX1 肿瘤患者,在这一亚型中,也发生端粒选择性延长。这些明显不同的结果掩盖了相似的临床表现和组织学,该结果与MEN1突变无关。这种强大的分子分型方法增加了对非功能性PNET相关细胞谱系的理解,能准确预测疾病进程,并可为术后临床决策提供依据。

研究人员表示,大多数胰腺神经内分泌肿瘤(PNET)不产生过量的激素,因此被认为是非功能性肿瘤。由于临床行为差异很大且远处转移最终致死,生物上的分类可指导治疗。

附:英文原文

Title: Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

Author: Paloma Cejas, Yotam Drier, Koen M. A. Dreijerink, Lodewijk A. A. Brosens, Vikram Deshpande, Charles B. Epstein, Elfi B. Conemans, Folkert H. M. Morsink, Mindy K. Graham, Gerlof D. Valk, Menno R. Vriens, Carlos Fernandez-del Castillo, Cristina R. Ferrone, Tomer Adar, Michaela Bowden, Holly J. Whitton, Annacarolina Da Silva, Alba Font-Tello, Henry W. Long, Elizabeth Gaskell, Noam Shoresh, Christopher M. Heaphy, Ewa Sicinska, Matthew H. Kulke, Daniel C. Chung, Bradley E. Bernstein, Ramesh A. Shivdasani

Issue&Volume: Volume 25 Issue 8, August 2019

Abstract: Most pancreatic neuroendocrine tumors (PNETs) do not produce excess hormones and are therefore considered non-functional13. As clinical behaviors vary widely and distant metastases are eventually lethal2,4, biological classifications might guide treatment. Using enhancer maps to infer gene regulatory programs, we find that non-functional PNETs fall into two major subtypes, with epigenomes and transcriptomes that partially resemble islet - and -cells. Transcription factors ARX and PDX1 specify these normal cells, respectively5,6, and 84% of 142 non-functional PNETs expressed one or the other factor, occasionally both. Among 103 cases, distant relapses occurred almost exclusively in patients with ARX+PDX1 tumors and, within this subtype, in cases with alternative lengthening of telomeres. These markedly different outcomes belied similar clinical presentations and histology and, in one cohort, occurred irrespective of MEN1 mutation. This robust molecular stratification provides insight into cell lineage correlates of non-functional PNETs, accurately predicts disease course and can inform postoperative clinical decisions.

DOI: 10.1038/s41591-019-0493-4

Source:https://www.nature.com/articles/s41591-019-0493-4

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Volume 25 Issue 8