Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment.
Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment.
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DOI：
10.1038/s41467-022-34011-3
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发表时间：
2022-10-21
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
嗜铬细胞瘤（PC）和副神经节瘤（PG）是罕见的神经内分泌肿瘤与自主神经。在这里，我们使用单核RNA-seq和大量组织基因表达数据来表征PCPG和正常肾上腺组织的细胞组成，细化肿瘤基因表达亚型，并进行临床和基因型关联。我们确认了7种PCPG基因表达亚型，具有显著的基因型和临床相关性。VHL、SDH编码基因（SDHx）或MAML 3融合突变的肿瘤的特征在于缺氧诱导因子信号传导和新血管生成。PCPG有少量浸润淋巴细胞，但有丰富的巨噬细胞。虽然肿瘤细胞在转录上类似于成熟的嗜铬细胞，但早期嗜铬细胞和成神经细胞标志物也是某些PCPG亚型的特征。转移性SDHX相关PCPG的基因表达谱表明这些肿瘤具有升高的细胞增殖和较低数量的非肿瘤性许旺细胞样细胞，而GPR 139是潜在的治疗诊断靶点。因此，我们的研究结果阐明了PCPG的不同转录程序和细胞组成，并确定了具有潜在临床意义的生物标志物。嗜铬细胞瘤和副神经节瘤（PCPG）是罕见的神经内分泌肿瘤。在这里，作者使用单核和大块组织RNA-seq来研究PCPG肿瘤及其微环境，并揭示分子亚型以及与转移相关的表达模式。
Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance. Pheochromocytomas and paragangliomas (PCPG) are rare neuroendocrine tumours. Here, the authors use single-nuclei and bulk-tissue RNA-seq to characterise PCPG tumours and their microenvironments and reveal molecular subtypes as well as expression patterns associated with metastasis.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
实现癌症基因组数据的共同愿景。
DOI：
10.1056/nejmp1607591
发表时间：
2016-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grossman RL;Heath AP;Ferretti V;Varmus HE;Lowy DR;Kibbe WA;Staudt LM
通讯作者：
Staudt LM
DOI：
10.1186/s13046-015-0278-7
发表时间：
2016-01-08
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Belkacemi L;Zhang SX
通讯作者：
Zhang SX
影响因子：
50.3
作者：
Fishbein L;Leshchiner I;Walter V;Danilova L;Robertson AG;Johnson AR;Lichtenberg TM;Murray BA;Ghayee HK;Else T;Ling S;Jefferys SR;de Cubas AA;Wenz B;Korpershoek E;Amelio AL;Makowski L;Rathmell WK;Gimenez-Roqueplo AP;Giordano TJ;Asa SL;Tischler AS;Cancer Genome Atlas Research Network;Pacak K;Nathanson KL;Wilkerson MD
通讯作者：
Wilkerson MD
影响因子：
16.6
作者：
Castro-Vega, Luis Jaime;Letouze, Eric;Burnichon, Nelly;Buffet, Alexandre;Disderot, Pierre-Helie;Khalifa, Emmanuel;Loriot, Celine;Elarouci, Nabila;Morin, Aurelie;Menara, Melanie;Lepoutre-Lussey, Charlotte;Badoual, Cecile;Sibony, Mathilde;Dousset, Bertrand;Libe, Rossella;Zinzindohoue, Franck;Plouin, Pierre Francois;Bertherat, Jerome;Amar, Laurence;de Reynies, Aurelien;Favier, Judith;Gimenez-Roqueplo, Anne-Paule
通讯作者：
Gimenez-Roqueplo, Anne-Paule