Journal article

Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer

RN Jorissen, M Christie, D Mouradov, A Sakthianandeswaren, S Li, C Love, ZZ Xu, PL Molloy, IT Jones, S McLaughlin, RL Ward, NJ Hawkins, AR Ruszkiewicz, J Moore, AW Burgess, D Busam, Q Zhao, RL Strausberg, L Lipton, J Desai Show all

British Journal of Cancer | Published : 2015

Abstract

Background:APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.Methods:APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort.Results:Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR≥1.79, P≤0.015; RFS HR≥1.8..

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Grants

Awarded by National Science Foundation


Funding Acknowledgements

We thank all individuals who participated in this study and colleagues who undertook sample and clinical data collection. We acknowledge the Victorian Cancer Biobank for the provision of specimens and BioGrid Australia for providing clinical data. This work was supported by a Cancer Australia Project Grant (APP1030098), a Cancer Council Victoria Grant-in-Aid (APP1060964), Ludwig Institute for Cancer Research, a Cancer Council Victoria Postgraduate Cancer Research Scholarship to MC and a National Health and Medical Research Council of Australia (NHMRC) R.D. Wright Biomedical Career Development Fellowship to OMS (APP1062226). This study was supported in part by the Victorian Government's Operational Infrastructure Support Program.