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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2016; 22(25): 5668-5677
Published online Jul 7, 2016. doi: 10.3748/wjg.v22.i25.5668
Genomic diversity of colorectal cancer: Changing landscape and emerging targets
Daniel H Ahn, Kristen K Ciombor, Sameh Mikhail, Tanios Bekaii-Saab
Daniel H Ahn, Tanios Bekaii-Saab, Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, United States
Kristen K Ciombor, Sameh Mikhail, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
Author contributions: All authors contributed to this paper with conception, drafting, revision and approval of the final version of the paper.
Conflict-of-interest statement: None of the authors have any potential conflicts of interest, and no financial support was used for the work of this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Tanios Bekaii-Saab, MD, Division of Medical Oncology, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ 85054, United States.
Telephone: +1-480-3424800 Fax: +1-480-3014675
Received: March 20, 2016
Peer-review started: March 22, 2016
First decision: May 12, 2016
Revised: May 20, 2016
Accepted: June 13, 2016
Article in press: June 13, 2016
Published online: July 7, 2016

Improvements in screening and preventive measures have led to an increased detection of early stage colorectal cancers (CRC) where patients undergo treatment with a curative intent. Despite these efforts, a high proportion of patients are diagnosed with advanced stage disease that is associated with poor outcomes, as CRC remains one of the leading causes of cancer-related deaths in the world. The development of next generation sequencing and collaborative multi-institutional efforts to characterize the cancer genome has afforded us with a comprehensive assessment of the genomic makeup present in CRC. This knowledge has translated into understanding the prognostic role of various tumor somatic variants in this disease. Additionally, the awareness of the genomic alterations present in CRC has resulted in an improvement in patient outcomes, largely due to better selection of personalized therapies based on an individual’s tumor genomic makeup. The benefit of various treatments is often limited, where recent studies assessing the genomic diversity in CRC have identified the development of secondary tumor somatic variants that likely contribute to acquired treatment resistance. These studies have begun to alter the landscape of treatment for CRC that include investigating novel targeted therapies, assessing the role of immunotherapy and prospective, dynamic assessment of changes in tumor genomic alterations that occur during the treatment of CRC.

Keywords: Colorectal cancer, KRAS mutation, BRAF mutation, Genomic diversity, Tumor DNA

Core tip: Tumor somatic variants have a prognostic role, in addition to treatment selection in patients with solid tumor malignancies, including colorectal cancer (CRC). The application of this knowledge in the development of novel, targeted therapies has resulted in improved patient outcomes in this disease. Our objective is to provide an overview of the genomic alterations present in CRC and its role in treatment implications, in addition to providing an overview of ongoing and future clinical trials.