Autophagy defects and related genetic variations in renal cell carcinoma with eosinophilic cytoplasmic inclusions.
Autophagy defects and related genetic variations in renal cell carcinoma with eosinophilic cytoplasmic inclusions.
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嗜酸性细胞质包涵体肾细胞癌的自噬缺陷及相关遗传变异
DOI：
10.1038/s41598-018-28369-y
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发表时间：
2018-07-02
影响因子：
4.6
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Yu Z;Ma J;Li X;Liu Y;Li M;Wang L;Zhao M;He H;Zhang Y;Rao Q;Zhao D;Wang Y;Fan L;Li P;Liu Y;Liu F;Zhang F;Ye J;Yan Q;Guo S;Wang Z
自噬和肿瘤之间的关系已被充分研究，但与自噬缺陷相关的肿瘤细胞形态学变化很少报道，特别是在肾细胞癌（RCC）中。我们收集了10例具有特征性嗜酸性细胞质内含物（ECIs）的肾肿瘤标本，发现ECIs主要由BRCA 1基因1（NBR 1）的邻居、PEX 14和CATALASE 1（CAT 1）的多核巨噬细胞1/P62组成。此外，透射电子显微镜分析显示，ECIs是蛋白质物质和过氧化物酶体的聚集体。这些结果证实了RCC中的ECIs是自噬缺陷的产物。ECIs的存在与RCC的高Fuhrman分级成分相关。全外显子组测序（WES）和桑格测序证实，具有ECIs的肿瘤显示自噬相关（ATG）基因（如ATG 7、ATG 5和ATG 10）的体细胞突变或高频率遗传变异。这些结果表明，ATG基因中的核苷酸变化与RCC中的自噬缺陷、ECI形成甚至肿瘤分级相关。
The relationship between autophagy and tumour is well studied, but tumour cell morphological changes associated with autophagy defects are rarely reported, especially in renal cell carcinoma (RCC). We collected 10 renal tumour samples with characteristic eosinophilic cytoplasmic inclusions (ECIs) and found that the ECIs were majorly composed of sequestosome 1/P62, neighbor of BRCA1 gene 1 (NBR1), PEX14, and CATALASE1 (CAT1). Further, transmission electron microscopy analysis revealed that ECIs were aggregates of proteinaceous material and peroxisomes. These results confirmed that ECIs in RCCs were the products of autophagy defects. The presence of ECIs was correlated with high Fuhrman grade components of RCCs. Whole-exome sequencing (WES) and Sanger sequencing confirmed that tumours with ECIs showed somatic mutations or high frequency of genetic variations in autophagy-related (ATG) genes, such as ATG7, ATG5, and ATG10. These results indicate that nucleotide changes in ATG genes are associated with autophagy defect, ECI formation, and even tumour grade in RCCs.
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DOI：
10.1016/j.biocel.2013.02.007
发表时间：
2013-05-01
影响因子：
4
作者：
Fu, Lei-lei;Cheng, Yan;Liu, Bo
通讯作者：
Liu, Bo
影响因子：
3.3
作者：
Krishnan, B;Truong, LD
通讯作者：
Truong, LD
影响因子：
16
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
13.3
作者：
Lebovitz CB;Robertson AG;Goya R;Jones SJ;Morin RD;Marra MA;Gorski SM
通讯作者：
Gorski SM