CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia

Susanne Pedersen, Susan Mitchell, Lloyd Graham, Aiden McEvoy, Melissa Thomas, Rohan Baker, Jason Ross, Zheng-Zhou Xu, Thu Ho, Lawrence LaPointe, Graeme Young, Peter Molloy

    Research output: Contribution to journalArticlepeer-review

    24 Citations (Scopus)

    Abstract

    The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously Loc100526820, is located on chromosome 6, hg19 chr6:163 834 097-163 834 982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific pcr (qMSP) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC. The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC.

    Original languageEnglish
    Pages (from-to)1071-1082
    Number of pages12
    JournalEpigenetics
    Volume9
    Issue number8
    DOIs
    Publication statusPublished - 6 May 2014

    Keywords

    • Biomarker
    • CAHM gene (LOC100526820)
    • Circulating DNA
    • Colorectal neoplasia
    • DNA methylation
    • Long non-coding RNA
    • QKI

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