SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer

NI Fleming; RN Jorissen; D Mouradov; M Christie; A Sakthianandeswaren; M Palmieri; F Day; S Li; C Tsui; L Lipton; J Desai; IT Jones; S McLaughlin; RL Ward; NJ Hawkins; AR Ruszkiewicz; J Moore; HJ Zhu; JM Mariadason; AW Burgess; D Busam; Q Zhao; RL Strausberg; P Gibbs; OM Sieber

Journal article

SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer

NI Fleming, RN Jorissen, D Mouradov, M Christie, A Sakthianandeswaren, M Palmieri, F Day, S Li, C Tsui, L Lipton, J Desai, IT Jones, S McLaughlin, RL Ward, NJ Hawkins, AR Ruszkiewicz, J Moore, HJ Zhu, JM Mariadason, AW Burgess Show all

Cancer Research | Published : 2013

DOI: 10.1158/0008-5472.CAN-12-2706

Abstract

Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis. Mutation spectra were compared between the genes, the pathogenicity of mutations was assessed, and relationships with clinicopathologic features were examined. The prevalence of SMAD4, SMAD2, and SMAD3..

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University of Melbourne Researchers

Michelle Palmieri Author

Jayesh Desai Author

Ian Jones Author

Antony Burgess Author

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Grants

Awarded by NHMRC

Funding Acknowledgements

The study was supported by the CSIRO Preventative Health Flagship through an Australian Cancer Grid Project Grant (L. Lipton, P. Gibbs, O.M. Sieber), the NHMRC through a Project Grant (Application ID 489418; L. Lipton, P. Gibbs, O.M. Sieber, R.L. Ward), a Program Grant (Application ID 487922; A. W. Burgess), the Hilton Ludwig Cancer Metastasis Initiative (L. Lipton, P. Gibbs, O.M. Sieber), the Victorian Government through a Victorian Cancer Agency Translation Cancer Research Grant (L. Lipton, P. Gibbs, O.M. Sieber), and the Operational Infrastructure Support Program. M. Christie and F. Day are supported by the Cancer Council Victoria through Postgraduate Cancer Research Scholarships and L. Lipton by the CSIRO Preventative Health Flagship through a Clinical Researcher Fellowship.