title: An investigation of the potential for epigenetic inactivation by transcription read-through in a sporadic colorectal cancer.
abstract: Aberrant transcription read-through of a gene promoter as a result of genetic structural rearrangements can cause the epigenetic inactivation of a neighbouring gene. All reported cases have involved copy number alterations that remove the 3' poly(A) transcription terminator sequence of a gene leading to transcription read-through (TRT) and methylation of the gene promoter of a downstream gene. We aimed to determine whether deletion of poly (A) transcription terminator sequences was associated with the methylation of neighbouring genes in a CRC with extensive copy number alterations. We performed a high resolution CGH array and methylation analysis on a CRC specimen to identify such alterations. Analysis of the CRC using high-resolution CGH identified 6 genes with deletions in the 3' part of the gene that encompassed the poly(A) transcription terminator sequence. Bisulphite sequencing of the promoter region of neighbouring (affected) genes at these six regions showed all candidate genes were unmethylated. Considering the fact that six TRT affected genes in a CRC with multiple deletions show no signs of hypermethylated promoters, it would be fairly appropriate to suggest that epigenetic inactivation by TRT might be a rare phenomenon in sporadic CRCs.
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia; Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad, India. Electronic address: sameers@mnnit.ac.in.
authors.forename: Sameer
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia; Department of Biology, Technical University of Darmstadt, Darmstadt, Germany.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Ludwig
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jason W H
authors.initials: JWH
authors.lastname: Wong
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Luke B
authors.initials: LB
authors.lastname: Hesson
mesh_terms: D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics*
keywords: DNA methylation; Epigenetic inactivation; Transcription read-through