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World J Clin Oncol. Dec 10, 2014; 5(5): 1036-1047
Published online Dec 10, 2014. doi: 10.5306/wjco.v5.i5.1036
Genomic era diagnosis and management of hereditary and sporadic colon cancer
Edward David Esplin, Michael Paul Snyder
Edward David Esplin, Michael Paul Snyder, Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, United States
Author contributions: Esplin ED and Snyder MP contributed to this paper.
Supported by The Child Health Research Institute and the Stanford CTSA, No. UL1 TR000093
Correspondence to: Edward David Esplin, MD, PhD, Clinical Scholar, Department of Genetics, Stanford University School of Medicine, 300 Pasteur Dr., Alway M302, Stanford, CA 94305, United States.
Telephone: +1-650-7239914 Fax: +1-650-7251534
Received: January 27, 2014
Revised: March 21, 2014
Accepted: May 16, 2014
Published online: December 10, 2014

The morbidity and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike. Despite current colonoscopy screening recommendations colorectal adenocarcinoma (CRC) still accounts for almost 140000 cancer cases yearly. Familial adenomatous polyposis (FAP) is a colon cancer predisposition due to alterations in the adenomatous polyposis coli gene, which is mutated in most CRC. Since the beginning of the genomic era next-generation sequencing analyses of CRC continue to improve our understanding of the genetics of tumorigenesis and promise to expand our ability to identify and treat this disease. Advances in genome sequence analysis have facilitated the molecular diagnosis of individuals with FAP, which enables initiation of appropriate monitoring and timely intervention. Genome sequencing also has potential clinical impact for individuals with sporadic forms of CRC, providing means for molecular diagnosis of CRC tumor type, data guiding selection of tumor targeted therapies, and pharmacogenomic profiles specifying patient specific drug tolerances. There is even a potential role for genomic sequencing in surveillance for recurrence, and early detection, of CRC. We review strategies for diagnostic assessment and management of FAP and sporadic CRC in the current genomic era, with emphasis on the current, and potential for future, impact of genome sequencing on the clinical care of these conditions.

Keywords: Colorectal adenocarcinoma, Familial adenomatous polyposis, Genome sequencing, Personalized medicine, Cancer genomics, Pharmacogenomics, Genomic medicine

Core tip: The era of genomic sequencing is beginning to make significant impact on the diagnosis and management of sporadic and inherited colorectal adenocarcinoma (CRC) such as familial adenomatous polyposis. This review will discuss the current guidelines for diagnosis and management of CRC and how genomic sequencing is enabling earlier definitive diagnosis with associated intensive surveillance and preventative interventions, molecular tumor characterization directing tumor specific therapy, germline patient genome analysis which informs individual drug tolerance and efficacy, and is evolving to develop post-treatment surveillance, with the potential to ultimately decrease the current prevalence and mortality of CRC, sporadic and hereditary.