title: Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.
abstract: Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, andBRAFmutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy.
authors.affiliation: Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: David G
authors.initials: DG
authors.lastname: Menter
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism; D014408:Biomarkers, Tumor; D003110:Colonic Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology*; D019175:DNA Methylation; D000069196:Gastrointestinal Microbiome; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D053842:Microsatellite Instability; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D001647:Bile Acids and Salts; D014408:Biomarkers, Tumor