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dc.contributor.authorSymonds, Erin
dc.contributor.authorPedersen, Susanne K
dc.contributor.authorMurray, David H
dc.contributor.authorJedi, Maher
dc.contributor.authorByrne, Susan E
dc.contributor.authorRabbitt, Philippa
dc.contributor.authorBaker, Rohan T
dc.contributor.authorBastin, Dawn
dc.contributor.authorYoung, Graeme Paul
dc.date.accessioned2018-06-25T02:46:50Z
dc.date.available2018-06-25T02:46:50Z
dc.date.issued2018-05-16
dc.identifier.citationSymonds, E. L., Pedersen, S. K., Murray, D. H., Jedi, M., Byrne, S. E., Rabbitt, P., … Young, G. P. (2018). Circulating tumour DNA for monitoring colorectal cancer—a prospective cohort study to assess relationship to tissue methylation, cancer characteristics and surgical resection. Clinical Epigenetics, 10(1). https://doi.org/10.1186/s13148-018-0500-5
dc.identifier.issn1868-7083
dc.identifier.urihttps://doi.org/10.1186/s13148-018-0500-5
dc.identifier.urihttp://hdl.handle.net/2328/38093
dc.description© The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.description.abstractAbstract Background Cell-free circulating tumour-derived DNA (ctDNA) can be detected by testing for methylated BCAT1 and IKZF1 DNA, which has proven sensitivity for colorectal cancer (CRC). A prospective correlative biomarker study between presence of methylated BCAT1 and IKZF1 in tissue and blood was conducted in cases with CRC to explore how detection of such ctDNA biomarkers relates to cancer characteristics, methylation in tissue and surgical resection of the primary cancer. Methods Enrolled patients with invasive CRC had blood collected at diagnosis, prior to any treatment or surgery (peri-diagnostic sample). A subgroup of patients also had cancer and adjacent non-neoplastic tissue collected at surgical resection, as well as a second blood sample collected within 12 months of surgery (post-surgery sample). DNA was extracted from all samples and assayed for methylated BCAT1 and IKZF1 to determine the degree of methylation in tissue and the presence of ctDNA in blood. Results Of 187 cases providing peri-diagnostic blood samples, tissue was available in 91, and 93 provided at least one post-surgery blood sample for marker analysis. Significant methylation of either BCAT1 or IKZF1 was seen in 86/91 (94.5%) cancer tissues, with levels independent of stage and higher than that observed in adjacent non-neoplastic specimens (P < 0.001). ctDNA methylated in BCAT1 or IKZF1 was detected in 116 (62.0%) cases at diagnosis and was significantly more likely to be detected with later stage (P < 0.001) and distal tumour location (P = 0.004). Of the 91 patients who provided pre-and post-surgery blood samples, 47 patients were ctDNA-positive at diagnosis and 35 (74.5%) became negative after tumour resection. Conclusion This study has shown that BCAT1 and IKZF1 methylation are common events in CRC with almost all cancer tissues showing significant levels of methylation in the two genes. The presence of ctDNA in blood is stage-related and show rapid reversion to negative following surgical resection. Monitoring methylated BCAT1 and IKZF1 levels could therefore inform adequacy of surgical resection. Trial registration Australian New Zealand Clinical Trial Registry number 12611000318987 . Registered 25 March 2011.en_US
dc.language.isoenen
dc.publisherBioMed Central
dc.relationhttp://purl.org/au-research/grants/nhmrc/1006242en
dc.relationhttp://purl.org/au-research/grants/nhmrc/1017083en
dc.rights© The Author(s). 2018
dc.subjectcolorectal cancer
dc.subjectCell-free circulating tumour-derived DNA
dc.subjectnon-neoplastic specimens
dc.subjectBCAT1 and IKZF1 methylation
dc.titleCirculating tumour DNA for monitoring colorectal cancer—a prospective cohort study to assess relationship to tissue methylation, cancer characteristics and surgical resection
dc.typeArticleen
dc.relation.grantnumberNHMRC/1006242en
dc.relation.grantnumberNHMRC/1017083en
dc.identifier.doihttps://doi.org/10.1186/s13148-018-0500-5
dc.date.updated2018-05-20T03:51:48Z
dc.rights.holderThe Author(s).
dc.rights.licenseCC-BY
local.contributor.authorOrcidLookupSymonds, Erin: https://orcid.org/0000-0003-2451-0358en_US


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