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Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Abstract

An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5'-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2(-DeltaCt) = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers.

Type Journal
ISBN 1947-6027 (Electronic) 1947-6019 (Linking)
Authors Graham, L. D.; Pedersen, S. K.; Brown, G. S.; Ho, T.; Kassir, Z.; Moynihan, A. T.; Vizgoft, E. K.; Dunne, R.; Pimlott, L.; Young, G. P.; Lapointe, L. C.; Molloy, P. L.;
Publisher Name Genes & Cancer
Published Date 2011-01-01 00:00:00
Published Volume 2
Published Issue 8
Published Pages 829-40
URL http://www.ncbi.nlm.nih.gov/pubmed/22393467
Status Published In-print