Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines.
Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines.
复制标题
遗传定义的散发性和遗传性1型乳头状肾细胞癌细胞系的特征。
DOI：
10.1002/gcc.22940
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Linehan WM
中科院分区：
文献类型：
--
作者：
Yang Y;Ricketts CJ;Vocke CD;Killian JK;Padilla-Nash HM;Lang M;Wei D;Lee YH;Wangsa D;Sourbier C;Meltzer PS;Ried T;Merino MJ;Metwalli AR;Ball MW;Srinivasan R;Linehan WM
肾细胞癌（RCC）不是一种单一的疾病，而是由几种不同的组织学定义的亚型组成，这些亚型与不同的遗传改变相关，需要亚型特异性管理和治疗。乳头状肾细胞癌（pRCC）是继常规/透明细胞RCC（ccRCC）之后的第二种最常见的亚型，占病例的约20%，并且被细分为1型和2型pRCC。对于临床前研究来说，拥有准确代表每个特定RCC亚型的细胞系是很重要的。这项研究表征了7种来源于1型pRCC原发和转移部位的细胞系，包括第一种来源于遗传性乳头状肾癌（HPRC）相关肿瘤的细胞系。在所有细胞系中观察到7号染色体的完全或部分获得，在几个细胞系中观察到16、17或20号染色体的其他常见获得。MET的激活突变存在于三种细胞系中，这些细胞系均表现出响应于HGF的MET磷酸化增加和响应于MET抑制剂的MET磷酸化消除。在所有细胞系模型中观察到由于突变或基因缺失导致的CDKN 2A丢失，与1型pRCC患者的不良结局相关。6个细胞系在无胸腺裸鼠中形成肿瘤异种移植物，从而提供1型pRCC的体内模型。这些1型pRCC细胞系提供了与pRCC相关的遗传改变的全面代表，这将使人们深入了解这种疾病的生物学，并成为治疗研究的理想临床前模型。
Renal cell carcinoma (RCC) is not a single disease but is made up of several different histologically defined subtypes that are associated with distinct genetic alterations which require subtype specific management and treatment. Papillary renal cell carcinoma (pRCC) is the second most common subtype after conventional/clear cell RCC (ccRCC), representing ~20% of cases, and is subcategorized into type 1 and type 2 pRCC. It is important for preclinical studies to have cell lines that accurately represent each specific RCC subtype. This study characterizes seven cell lines derived from both primary and metastatic sites of type 1 pRCC, including the first cell line derived from a hereditary papillary renal carcinoma (HPRC)‐associated tumor. Complete or partial gain of chromosome 7 was observed in all cell lines and other common gains of chromosomes 16, 17, or 20 were seen in several cell lines. Activating mutations of MET were present in three cell lines that all demonstrated increased MET phosphorylation in response to HGF and abrogation of MET phosphorylation in response to MET inhibitors. CDKN2A loss due to mutation or gene deletion, associated with poor outcomes in type 1 pRCC patients, was observed in all cell line models. Six cell lines formed tumor xenografts in athymic nude mice and thus provide in vivo models of type 1 pRCC. These type 1 pRCC cell lines provide a comprehensive representation of the genetic alterations associated with pRCC that will give insight into the biology of this disease and be ideal preclinical models for therapeutic studies.
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影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
DOI：
10.1038/nrurol.2010.47
发表时间：
2010-05
期刊：
Nature reviews. Urology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.8
作者：
Schmidt, L;Duh, FM;Zbar, B
通讯作者：
Zbar, B
影响因子：
6
作者：
Jiang, F;Richter, J;Moch, H
通讯作者：
Moch, H
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ