title: Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis.
abstract: 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.
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Eri
authors.initials: E
authors.lastname: Arai
authors.forename: Suenori
authors.initials: S
authors.lastname: Chiku
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Hiramoto
authors.forename: Takao
authors.initials: T
authors.lastname: Nammo
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D050939:Gene Fusion; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger