Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis.
Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis.
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DOI：
10.1002/gcc.22211
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发表时间：
2014-12
影响因子：
3.7
通讯作者：
Kanai, Yae
中科院分区：
文献类型：
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作者：
Gotoh, Masahiro;Ichikawa, Hitoshi;Arai, Eri;Chiku, Suenori;Sakamoto, Hiromi;Fujimoto, Hiroyuki;Hiramoto, Masaki;Nammo, Takao;Yasuda, Kazuki;Yoshida, Teruhiko;Kanai, Yae
本研究的目的是阐明嵌合体转录本的表达在肾癌发生中的作用。对从初始队列中的68名透明细胞肾细胞癌（RCC）患者获得的68份癌组织标本（T）和11份非癌肾皮质组织标本（N）进行全转录组分析（RNA测序）和使用depletion程序探索候选嵌合转录物。作为阳性对照，分析了与Xp11.2易位相关的两个RCC。经逆转录-PCR和桑格测序验证后，在68例透明细胞RCC中的17例（25%）中鉴定出26个新的嵌合体转录本。在五个嵌合转录物中确定基因组断裂点。定量RT-PCR分析揭示了MMAHC、PTER、EPC 2、ATXN 7、FHIT、KIFAP 3、CPEB 1、MINPP 1、TEX 264、FAM 107 A、UPF 3A、CDC 16、MCCC 1、CPSF 3和ASAP 2基因的mRNA表达水平，这些基因是参与初始组中嵌合转录物的伴侣基因，相对于第二组群中相应的26个N样品，26个T样品中的显著降低。此外，T样本中上述伴侣基因的mRNA表达水平与肿瘤侵袭性和较差的患者结局显著相关，表明这些基因的表达降低可能参与RCC的恶性进展。当它们的表达水平降低时，这些伴侣基因在参与嵌合转录物时也可能不完全起作用。这些数据表明，嵌合转录本的产生可能通过诱导肿瘤相关基因的功能障碍参与肾癌的发生。
The aim of this study was to clarify the participation of expression of chimeric transcripts in renal carcinogenesis. Whole transcriptome analysis (RNA sequencing) and exploration of candidate chimeric transcripts using the deFuse program were performed on 68 specimens of cancerous tissue (T) and 11 specimens of non-cancerous renal cortex tissue (N) obtained from 68 patients with clear cell renal cell carcinomas (RCCs) in an initial cohort. As positive controls, two RCCs associated with Xp11.2 translocation were analyzed. After verification by reverse transcription (RT)-PCR and Sanger sequencing, 26 novel chimeric transcripts were identified in 17 (25%) of the 68 clear cell RCCs. Genomic breakpoints were determined in five of the chimeric transcripts. Quantitative RT-PCR analysis revealed that the mRNA expression levels for the MMACHC, PTER, EPC2, ATXN7, FHIT, KIFAP3, CPEB1, MINPP1, TEX264, FAM107A, UPF3A, CDC16, MCCC1, CPSF3, and ASAP2 genes, being partner genes involved in the chimeric transcripts in the initial cohort, were significantly reduced in 26 T samples relative to the corresponding 26 N samples in the second cohort. Moreover, the mRNA expression levels for the above partner genes in T samples were significantly correlated with tumor aggressiveness and poorer patient outcome, indicating that reduced expression of these genes may participate in malignant progression of RCCs. As is the case when their levels of expression are reduced, these partner genes also may not fully function when involved in chimeric transcripts. These data suggest that generation of chimeric transcripts may participate in renal carcinogenesis by inducing dysfunction of tumor-related genes.
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影响因子：
82.9
作者：
Kohno T;Ichikawa H;Totoki Y;Yasuda K;Hiramoto M;Nammo T;Sakamoto H;Tsuta K;Furuta K;Shimada Y;Iwakawa R;Ogiwara H;Oike T;Enari M;Schetter AJ;Okayama H;Haugen A;Skaug V;Chiku S;Yamanaka I;Arai Y;Watanabe S;Sekine I;Ogawa S;Harris CC;Tsuda H;Yoshida T;Yokota J;Shibata T
通讯作者：
Shibata T
影响因子：
9.8
作者：
Helmlinger D;Hardy S;Abou-Sleymane G;Eberlin A;Bowman AB;Gansmüller A;Picaud S;Zoghbi HY;Trottier Y;Tora L;Devys D
通讯作者：
Devys D
影响因子：
3.9
作者：
Jarjanazi, Hamdi;Kiefer, Jeffrey;Ozcelik, Hilmi
通讯作者：
Ozcelik, Hilmi
影响因子：
5.2
作者：
Karras JR;Paisie CA;Huebner K
通讯作者：
Huebner K
影响因子：
64.8
作者：
通讯作者：
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