Comparative proteogenomic analysis of right-sided colon cancer, left-sided colon cancer and rectal cancer reveals distinct mutational profiles

• Authors: Robin Imperial, University of Missouri; Zaheer Ahmed, University of Missouri; Omer M. Toor, University of Missouri; Cihat Erdogan, Namik Kemal University; Ateeq Khaliq, University of Missouri; Paul Case, University of Missouri; James Case, St Lukes Health System Kansas City; Kevin Kennedy, St Lukes Hospital; Lee S. Cummings, University of Missouri; Niklas Melton, Missouri University of Science & Technology; Shahzad Raza, University of Missouri; Banu Diri, Yildiz Technical University; Ramzi Mohammad, Wayne State University; Bassel El-Rayes, Emory University; Timothy Pluard, University of Missouri; Arif Hussain, University of Maryland; Janakiraman Subramanian, University of Missouri; Ashiq Masood, Rush University
• Journal Title: Molecular Cancer
• Volume: Volume 17, Number 1
• Publisher: BMC (part of Springer Nature) | 2018-12-21, Pages 177-177
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s12943-018-0923-9
• Subjects: Health Sciences, Oncology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Oncology; Right-sided colon cancer; Left-sided colon cancer; Rectal cancers; Clonal evolution; Proteomics; Hotspot mutations

Abstract

Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450∗specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors.