Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.
Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.
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DOI：
10.1186/1471-2407-10-196
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发表时间：
2010-05-12
期刊：
影响因子：
3.8
通讯作者：
Teh BT
中科院分区：
文献类型：
--
作者：
Tan MH;Wong CF;Tan HL;Yang XJ;Ditlev J;Matsuda D;Khoo SK;Sugimura J;Fujioka T;Furge KA;Kort E;Giraud S;Ferlicot S;Vielh P;Amsellem-Ouazana D;Debré B;Flam T;Thiounn N;Zerbib M;Benoît G;Droupy S;Molinié V;Vieillefond A;Tan PH;Richard S;Teh BT
肾嫌色细胞癌（chRCC）和肾嗜酸细胞瘤是两个不同的，但密切相关的实体有很强的形态和遗传相似性。虽然chRCC是恶性肿瘤，但嗜酸细胞瘤通常被认为是良性实体。共同的细胞起源最好地解释了重叠的特征，因此，chRCC和嗜酸细胞瘤之间的生物学差异在致癌作用、诊断和临床管理方面具有相当大的意义。以往的研究在检查嗜酸细胞瘤和嫌色细胞肾癌之间的差异方面相对有限。将使用Affytelium HGU 133 Plus 2平台的基因表达谱应用于chRCC（n = 15）和嗜酸细胞瘤标本（n = 15）。应用监督分析来鉴定歧视性基因签名以及差异表达的基因。高通量单核苷酸多态性（SNP）基因分型进行独立的样品（n = 14），使用Affyssin基因芯片映射100 K阵列，以评估表达和基因拷贝数之间的相关性。在一组独立的肿瘤中进行免疫组织化学验证。开发了一种新的14探针组签名，以93%的准确率对肿瘤进行内部分类，并在外部数据集上成功验证，准确率为94%。通路分析强调了chRCC中c-erbB 2和哺乳动物雷帕霉素靶蛋白（mTOR）信号传导的临床相关失调通路，但在免疫组织化学上未发现p-AKT或细胞外HER 2表达的显著差异。在细胞遗传学和表达分析中均反映出染色体1 p的丢失，这对两种实体都是常见的，这意味着这可能是组织发生中的早期事件。多个区域的细胞遗传学改变和相应的表达偏差区分这两个实体进行了鉴定。副纤维蛋白、水通道蛋白6和突触回蛋白3是新的免疫组化标记物，可有效区分两种病理实体。基因表达谱、高通量SNP基因分型和通路分析有效地区分了chRCC和嗜酸细胞瘤。我们已经产生了一种新的转录预测，能够准确地区分这两个实体，并已在内部和独立的数据集验证，这意味着概括性。一个细胞遗传学改变，染色体1 p的丢失，共同肾嗜酸细胞瘤和chRCC已被确定，提供了机会，确定新的肿瘤抑制基因，我们已经确定了一系列的免疫组化标记，是临床上有用的区分chRCC和嗜酸细胞瘤。
Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
影响因子：
8
作者：
Takahashi, M;Yang, XMJ;Teh, BT
通讯作者：
Teh, BT
影响因子：
8
作者：
Zhao, J.;Yart, A.;Moch, H.
通讯作者：
Moch, H.
影响因子：
3.4
作者：
Oxley, J. D.;Sullivan, J.;Gillatt, D. A.
通讯作者：
Gillatt, D. A.