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Identification of protein-coding and intronic noncoding RNAs down-regulated in clear cell renal carcinoma

ABSTRACT: The clear cell subtype of renal cell carcinoma (RCC) is the most lethal and prevalent cancer of the urinary system. To investigate the molecular changes associated with malignant transformation in clear cell RCC, the gene expression profiles of matched samples of tumor and adjacent non-neoplastic tissue were obtained from 6 patients. A custom-built cDNA microarray platform was used, comprising 2,292 probes that map to exons of genes and 822 probes for noncoding RNAs mapping to intronic regions. Intronic transcription was detected in all normal and neoplastic renal tissues. A subset of 55 transcripts was significantly down-regulated in clear cell RCC relative to the matched non-tumor tissue as determined by a combination of two statistical tests and leave-one-out patient cross-validation. Among the down-regulated transcripts, 49 mapped to untranslated or coding exons and 6 were intronic relative to known exons of protein-coding genes. Lower levels of expression of SIN3B, TRIP3, SYNJ2BP and NDE1 (p < 0.02), and of intronic transcripts derived from SND1 and ACTN4 loci (p < 0.05), were confirmed in clear cell RCC by Real-time RT-PCR. A subset of 25 transcripts was deregulated in additional 6 non-clear cell RCC samples, pointing to common transcriptional alterations in RCC irrespective of the histological subtype or differentiation state of the tumor. Our results indicate a novel set of tumor suppressor gene candidates, including noncoding intronic RNAs, which may play a significant role in malignant transformations of normal renal cells. Keywords: Disease state analysis Overall design: Fluorescently labeled cDNA targets derived from tumor and non-tumor tissue from each patient were combined and hybridized to spotted cDNA microarrays. For each patient, a replicate hybridization with dye-swap of labeled targets was performed. For each tissue (tumor and adjacent non-tumor tissue), there are 4 replicate mesurements for each probe.

INSTRUMENT(S): IQUSP_Human_intronic_4k_v2.0

ORGANISM(S): Homo sapiens  

SUBMITTER: Glauber Costa Brito  

PROVIDER: GSE7367 | GEO | 2008-03-25



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