title: CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia.
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.
authors.affiliation: Clinical Genomics Pty Ltd; North Ryde, NSW Australia.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Pedersen
authors.affiliation: CSIRO Preventative Health Flagship; Animal, Food & Health Sciences Division; North Ryde, NSW Australia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Mitchell
authors.affiliation: CSIRO Preventative Health Flagship; Animal, Food & Health Sciences Division; North Ryde, NSW Australia.
authors.forename: Lloyd D
authors.initials: LD
authors.lastname: Graham
authors.affiliation: Clinical Genomics Pty Ltd; North Ryde, NSW Australia.
authors.forename: Aidan
authors.initials: A
authors.lastname: McEvoy
authors.affiliation: Clinical Genomics Pty Ltd; North Ryde, NSW Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Thomas
authors.affiliation: Clinical Genomics Pty Ltd; North Ryde, NSW Australia.
authors.forename: Rohan T
authors.initials: RT
authors.lastname: Baker
authors.affiliation: CSIRO Preventative Health Flagship; Animal, Food & Health Sciences Division; North Ryde, NSW Australia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Ross
authors.affiliation: CSIRO Preventative Health Flagship; Animal, Food & Health Sciences Division; North Ryde, NSW Australia.
authors.forename: Zheng-Zhou
authors.initials: ZZ
authors.lastname: Xu
authors.affiliation: CSIRO Preventative Health Flagship; Animal, Food & Health Sciences Division; North Ryde, NSW Australia.
authors.forename: Thu
authors.initials: T
authors.lastname: Ho
authors.affiliation: Clinical Genomics Pty Ltd; North Ryde, NSW Australia.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: LaPointe
authors.affiliation: Flinders Centre for Innovation in Cancer; Flinders University (FMC); Adelaide, SA Australia.
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.affiliation: CSIRO Preventative Health Flagship; Animal, Food & Health Sciences Division; North Ryde, NSW Australia.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Molloy
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018938:Caco-2 Cells; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C000599423:CAHM long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: Biomarker; CAHMgene (LOC100526820); DNA methylation; Long non-coding RNA; QKI; circulating DNA; colorectal neoplasia