@article{20f6a50790da46fbb8c2af5d64339b39,
title = "Tetranucleotide and low microsatellite instability are inversely associated with the cpg island methylator phenotype in colorectal cancer",
abstract = "MSH3 gene or protein deficiency or loss-of-function in colorectal cancer can cause a DNA mismatch repair defect known as “elevated microsatellite alterations at selected tetranucleotide repeats” (EMAST). A high percentage of MSI-H tumors exhibit EMAST, while MSI-L is also linked with EMAST. However, the distribution of CpG island methylator phenotype (CIMP) within the EMAST spectrum is not known. Five tetranucleotide repeat and five MSI markers were used to classify 100 sporadic colorectal tumours for EMAST, MSI-H and MSI-L according to the number of unstable markers detected. Promoter methylation was determined using methylation-specific PCR for MSH3, MCC, CDKN2A (p16) and five CIMP marker genes. EMAST was found in 55% of sporadic colorectal carcinomas. Carcinomas with only one positive marker (EMAST-1/5, 26%) were associated with advanced tumour stage, increased lymph node metastasis, MSI-L and lack of CIMP-H. EMAST-2/5 (16%) carcinomas displayed some methylation but MSI was rare. Carcinomas with ≥3 positive EMAST markers (13%) were more likely to have a proximal colon location and be MSI-H and CIMP-H. Our study suggests that EMAST/MSI-L is a valuable prognostic and predictive marker for colorectal carcinomas that do not display the high methylation phenotype CIMP-H.",
keywords = "CDKN2A, CIMP, Colorectal cancer, EMAST, MCC, MSH3, MSI-H, MSI-L",
author = "Sabine Meessen and Nicola Currey and Zeenat Jahan and Parker, {Hannah W.} and Jenkins, {Mark A.} and Buchanan, {Daniel D.} and Hopper, {John L.} and Eva Segelov and Dahlstrom, {Jane E.} and Kohonen-Corish, {Maija R.J.}",
note = "Funding Information: This research was funded by the National Health and Medical Research Council of Australia (NHMRC) grant number 1020406, Cancer Council NSW grants RG17-05 and RG19-01, and the Gastroenterological Society of Australia GESA Project Grant. The Australasian Colorectal Cancer Family Registry (ACCFR) is supported in part by funding from the National Cancer Institute (NCI) of the U.S. National Institutes of Health (NIH), grant number U01 CA167551.Acknowledgments: We thank Andrew Biankin, Robyn Ward, Nicholas Hawkins, South Western Sydney Colorectal Tumour Group, South Western Sydney Clinical Cancer Registry, Australian Pancreatic Cancer Genome Initiative, the Australasian Colorectal Cancer Family Registry at the University of Melbourne and UNSW Biorepository at Mark Wainwright Analytical Centre UNSW Sydney for providing patient tissue, DNA specimens and data. We thank Owen Dent for advice with statistics. The ACCFR wishes to thank the generous contributions of their study participants, dedication of study staff, and the financial support from the U.S. National Cancer Institute, without which their registry would not exist. Funding Information: Funding: This research was funded by the National Health and Medical Research Council of Australia (NHMRC) grant number 1020406, Cancer Council NSW grants RG17-05 and RG19-01, and the Gastroenterological Society of Australia GESA Project Grant. The Australasian Colorectal Cancer Family Registry (ACCFR) is supported in part by funding from the National Cancer Institute (NCI) of the U.S. National Institutes of Health (NIH), grant number U01 CA167551. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jul,
day = "2",
doi = "10.3390/cancers13143529",
language = "English",
volume = "13",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI AG",
number = "14",
}
