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

Lloyd Graham, Susanne Pedersen, Glenn Brown, Thu Ho, Zena Kassir, Audrey Moynihan, Emma Vizgoft, Robert Dunne, Letitia Pimlott, Graeme Young, Lawrence Lapointe, Peter Molloy

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    165 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)829-840
    Number of pages12
    JournalGenes & Cancer
    Volume2
    Issue number8
    DOIs
    Publication statusPublished - Aug 2011

    Keywords

    • colorectal adenoma
    • colorectal cancer
    • colorectal neoplasia
    • CRNDE
    • RNA biomarker

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