title: 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(-ΔCt) = 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.
authors.affiliation: CSIRO Food and Nutritional Sciences, Sydney, NSW, Australia.
authors.forename: Lloyd D
authors.initials: LD
authors.lastname: Graham
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Pedersen
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Brown
authors.forename: Thu
authors.initials: T
authors.lastname: Ho
authors.forename: Zena
authors.initials: Z
authors.lastname: Kassir
authors.forename: Audrey T
authors.initials: AT
authors.lastname: Moynihan
authors.forename: Emma K
authors.initials: EK
authors.lastname: Vizgoft
authors.forename: Robert
authors.initials: R
authors.lastname: Dunne
authors.forename: Letitia
authors.initials: L
authors.lastname: Pimlott
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Lapointe
authors.forename: Peter L
authors.initials: PL
authors.lastname: Molloy