Defining the origin, evolution, and immune composition of SDH-deficient renal cell carcinoma.
Defining the origin, evolution, and immune composition of SDH-deficient renal cell carcinoma.
复制标题
DOI：
10.1016/j.isci.2022.105389
复制
发表时间：
2022-11-18
期刊：
影响因子：
5.8
通讯作者：
Mitchell, Thomas
中科院分区：
文献类型：
--
作者：
Neves, Joana B.;Roberts, Kirsty;Nguyen, Janani Sivakumaran;El Sheikh, Soha;Tran-Dang, My-Anh;Horsfield, Catherine;Mumtaz, Faiz;Campbell, Peter;Stauss, Hans;Tran, Maxine G. B.;Mitchell, Thomas
琥珀酸脱氢酶（SDH）缺陷型肾细胞癌是一种罕见的遗传性肾癌亚型。临床诊断可能具有挑战性，并且几乎没有证据可以指导系统性治疗选择。我们通过分析全基因组、转录组以及流式细胞术和免疫组织化学对一组肿瘤进行了基因组分析，以更深入地了解其分子生物学。我们发现早期肿瘤激活后的中性演变缺乏次要驱动事件。我们发现这些肿瘤有上皮来源，可能来自致密斑，一个专门的旁分泌细胞的肾肾小球。它们随后发展成为免疫排斥肿瘤。我们提供了一个高度特异性的肿瘤标志物PAPPA 2的转录组学和蛋白质表达证据。这些翻译结果对这种罕见肿瘤亚型的诊断和治疗具有重要意义。全基因组测序表明早期启动，随后是中性进化保留的转录信号揭示了一个假定的致密斑细胞起源免疫表型分析表明免疫排斥的微环境PAPPA 2显示出作为高度特异性肿瘤标志物的有前途的实用性癌症系统生物学;癌症;基因组学
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma represents a rare subtype of hereditary kidney cancer. Clinical diagnosis can be challenging and there is little evidence to guide systemic therapeutic options. We performed genomic profiling of a cohort of tumors through the analysis of whole genomes, transcriptomes, as well as flow cytometry and immunohistochemistry in order to gain a deeper understanding of their molecular biology. We find neutral evolution after early tumor activation with a lack of secondary driver events. We show that these tumors have epithelial derivation, possibly from the macula densa, a specialized paracrine cell of the renal juxtaglomerular apparatus. They subsequently develop into immune excluded tumors. We provide transcriptomic and protein expression evidence of a highly specific tumor marker, PAPPA2. These translational findings have implications for the diagnosis and treatment for this rare tumor subtype. Whole genome sequencing indicates early initiation followed by neutral evolution Retained transcriptional signals uncovers a putative macula densa cell of origin Immunophenotyping demonstrates an immune-excluded microenvironment PAPPA2 shows promising utility as a highly specific tumor marker Cancer systems biology; Cancer; Genomics
登录
查看更多内容
影响因子：
13.6
作者：
Chen, Lihe;Chou, Chun-Lin;Knepper, Mark A.
通讯作者：
Knepper, Mark A.
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
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：
10.3
作者：
Heitzeneder, Sabine;Sotillo, Elena;Mackall, Crystal L.
通讯作者：
Mackall, Crystal L.
影响因子：
158.5
作者：
Choueiri, T. K.;Tomczak, P.;Powles, T.
通讯作者：
Powles, T.