Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis

作者: Masahiro Gotoh , Hitoshi Ichikawa , Eri Arai , Suenori Chiku , Hiromi Sakamoto

DOI: 10.1002/GCC.22211

关键词: Sanger sequencingFHITGeneFusion geneBiologyTranscriptomeReverse transcriptaseMolecular biologyGene expression profilingClear cell

摘要: The aim of this study was to clarify the participation expression chimeric transcripts in renal carcinogenesis. Whole transcriptome analysis (RNA sequencing) and exploration candidate using deFuse program were performed on 68 specimens cancerous tissue (T) 11 non-cancerous cortex (N) obtained from patients with clear cell carcinomas (RCCs) an initial cohort. As positive controls, two RCCs associated Xp11.2 translocation analyzed. After verification by reverse transcription (RT)-PCR Sanger sequencing, 26 novel identified 17 (25%) RCCs. Genomic breakpoints determined five transcripts. Quantitative RT-PCR revealed that mRNA levels for MMACHC, PTER, EPC2, ATXN7, FHIT, KIFAP3, CPEB1, MINPP1, TEX264, FAM107A, UPF3A, CDC16, MCCC1, CPSF3, ASAP2 genes, being partner genes involved cohort, significantly reduced T samples relative corresponding N second Moreover, above correlated tumor aggressiveness poorer patient outcome, indicating these may participate malignant progression is case when their are reduced, also not fully function These data suggest generation carcinogenesis inducing dysfunction tumor-related genes.

参考文章(55)
Jamie A Davies, Vladimir L Buchman, Olga Krylova, Natalia N Ninkina, Molecular cloning and expression pattern of rpr-1, a resiniferatoxin-binding, phosphotriesterase-related protein, expressed in rat kidney tubules. FEBS Letters. ,vol. 410, pp. 378- 382 ,(1997) , 10.1016/S0014-5793(97)00614-5
Emiko Sugawara, Yuki Togashi, Naoto Kuroda, Seiji Sakata, Satoko Hatano, Reimi Asaka, Takeshi Yuasa, Junji Yonese, Masanobu Kitagawa, Hiroyuki Mano, Yuichi Ishikawa, Kengo Takeuchi, Identification of Anaplastic Lymphoma Kinase Fusions in Renal Cancer Large-Scale Immunohistochemical Screening by the Intercalated Antibody-Enhanced Polymer Method Cancer. ,vol. 118, pp. 4427- 4436 ,(2012) , 10.1002/CNCR.27391
Yae Kanai, Saori Ushijima, Hiroyuki Fujimoto, Kiyoshi Mukai, Setsuo Hirohashi, Eri Arai, Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissues. International Journal of Cancer. ,vol. 119, pp. 288- 296 ,(2006) , 10.1002/IJC.21807
Adrián Mariño-Enríquez, Wen-Bin Ou, Christopher B. Weldon, Jonathan A. Fletcher, Antonio R. Pérez-Atayde, ALK rearrangement in sickle cell trait‐associated renal medullary carcinoma Genes, Chromosomes and Cancer. ,vol. 50, pp. 146- 153 ,(2011) , 10.1002/GCC.20839
Hamdi Jarjanazi, Jeffrey Kiefer, Sevtap Savas, Laurent Briollais, Sukru Tuzmen, Noel Pabalan, Irada Ibrahim-Zada, Spyro Mousses, Hilmi Ozcelik, Discovery of genetic profiles impacting response to chemotherapy: application to gemcitabine. Human Mutation. ,vol. 29, pp. 461- 467 ,(2008) , 10.1002/HUMU.20732
Jinfang Zhang, Lixin Wan, Xiangpeng Dai, Yi Sun, Wenyi Wei, Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis. Biochimica et Biophysica Acta. ,vol. 1845, pp. 277- 293 ,(2014) , 10.1016/J.BBCAN.2014.02.001
Ao Li, Zongzhi Liu, Kimberly Lezon-Geyda, Sudipa Sarkar, Donald Lannin, Vincent Schulz, Ian Krop, Eric Winer, Lyndsay Harris, David Tuck, GPHMM: an integrated hidden Markov model for identification of copy number alteration and loss of heterozygosity in complex tumor samples using whole genome SNP arrays Nucleic Acids Research. ,vol. 39, pp. 4928- 4941 ,(2011) , 10.1093/NAR/GKR014
Takashi Kohno, Hitoshi Ichikawa, Yasushi Totoki, Kazuki Yasuda, Masaki Hiramoto, Takao Nammo, Hiromi Sakamoto, Koji Tsuta, Koh Furuta, Yoko Shimada, Reika Iwakawa, Hideaki Ogiwara, Takahiro Oike, Masato Enari, Aaron J Schetter, Hirokazu Okayama, Aage Haugen, Vidar Skaug, Suenori Chiku, Itaru Yamanaka, Yasuhito Arai, Shun-ichi Watanabe, Ikuo Sekine, Seishi Ogawa, Curtis C Harris, Hitoshi Tsuda, Teruhiko Yoshida, Jun Yokota, Tatsuhiro Shibata, KIF5B-RET fusions in lung adenocarcinoma Nature Medicine. ,vol. 18, pp. 375- 377 ,(2012) , 10.1038/NM.2644
Z-H Zhu, Y P Yu, Y-K Shi, J B Nelson, J-H Luo, CSR1 induces cell death through inactivation of CPSF3. Oncogene. ,vol. 28, pp. 41- 51 ,(2009) , 10.1038/ONC.2008.359