Colon Cancer Tumor Location Defined by Gene Expression May Disagree With Anatomic Tumor Location |
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| Affiliation: | 1. Georges Pompidou European Hospital, Department of Hepatogastroenterology and GI Oncology, Sorbonne Paris Cité/Université Paris Descartes, 75015 Paris, France;1. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan;2. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan;1. Department of Surgical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse (IUCT), Oncopole, Toulouse, France;2. INSERM CRCT 19, Toulouse, France;3. Biostatistics Unit, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse (IUCT), Oncopole, Toulouse, France;4. Department of Radiology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse (IUCT), Oncopole, Toulouse, France;5. INSERM CRCT 1, Toulouse, France;6. Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse (IUCT), Oncopole, Toulouse, France;7. Department of Surgical Oncology, CRLCC Jean Perrin, Clermont-Ferrand, France;1. Cancer Research Centre, Cancer Council Queensland, Brisbane, Australia;2. School of Public Health and Social Work, Queensland University of Technology, Kelvin Grove, Brisbane QLD 4059, Australia;3. Cancer Research Division, Cancer Council New South Wales, Kings Cross, NSW 1340, Australia;4. Sydney School of Public Health, University of Sydney, NSW 2006, Australia;5. Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Parklands Drive, Southport QLD 4222, Australia;6. School of Mathematical Sciences, Queensland University of Technology, Gardens Point, Brisbane QLD 4000, Australia;1. Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas;2. Division of Medical Oncology, Department of Medicine, Baylor College of Medicine, Houston, Texas;3. Division of Surgical Oncology, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas;4. Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas |
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| Abstract: | BackgroundCancers of the right colon have been shown to differ from left-side colon cancers in prognosis, response to epithelial growth factor receptor inhibitors, microsatellite instability and BRAF mutation status, and other molecular characteristics. Clinical application of these differences will benefit from a deeper understanding of how tumor location defines and is defined by gene expression.Materials and MethodsThis study was carried out using Affymetrix microarray datasets (Cohort A: training set, n = 352; validation set, n = 519) and samples from The Cancer Genome Atlas Colon Adenocarcinoma database (Cohort B: n = 408), in which tumor location was reported. Gene expression patterns characteristic of tumor side were identified in a manner unbiased by statistical classification method.ResultsIn the Cohort A validation set, the anatomic locations of 75% of tumors agree with the locations predicted by gene expression (so-called genomic location), whereas 8% of tumors had genomic locations discordant with their anatomic locations, and 17% of tumors had ambiguous genomic locations. Genomic location was a better predictor of microsatellite instability, CpG island methylator phenotype status, and BRAF mutation status than anatomic location. Tumors with ambiguous genomic location were significantly (P = 1.3 × 10−7) more likely to have the mesenchymal consensus molecular subtype (40%) than those with a specific genomic location (18%). A genomic signature to predict genomic location was defined.ConclusionTumor location is increasingly considered in deciding treatment of a colon tumor. We showed that genomic location was superior to anatomic location as a predictor of molecular characteristics, suggesting that it may be a more accurate predictor of response. |
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| Keywords: | Genomic signature Left-side colon cancer Molecular classification Right-side colon cancer Tumor sidedness |
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