Comparative proteogenomic analysis of right-sided colon cancer, left-sided colon cancer and rectal cancer reveals distinct mutational profiles
| Autor: | Ashiq Masood, Omer M Toor, Janakiraman Subramanian, Arif Hussain, Cihat Erdogan, Zaheer Ahmed, Shahzad Raza, Timothy J. Pluard, Kevin F. Kennedy, Banu Diri, James Brett Case, Paul Case, Ateeq Khaliq, Robin Imperial, Ramzi M. Mohammad, Bassel F. El-Rayes, Lee S. Cummings, Niklas Melton |
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| Rok vydání: | 2018 |
| Předmět: |
Proteomics
0301 basic medicine Cancer Research Carcinogenesis Somatic cell Colorectal cancer In silico Nonsense mutation Biology medicine.disease_cause lcsh:RC254-282 Rectal cancers Somatic evolution in cancer Right-sided colon cancer 03 medical and health sciences 0302 clinical medicine Left-sided colon cancer medicine Humans Letter to the Editor Gene Proteogenomics Clonal evolution Rectal Neoplasms lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease humanities 030104 developmental biology Oncology Hotspot mutations 030220 oncology & carcinogenesis Colonic Neoplasms Mutation Cancer research Molecular Medicine KRAS |
| Zdroj: | Molecular Cancer Molecular Cancer, Vol 17, Iss 1, Pp 1-7 (2018) |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/s12943-018-0923-9 |
| Popis: | 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. Merit Review Award, Medical Research Service, Department of Veterans AffairsUS Department of Veterans Affairs [I01 BX000545]; Veterans AffairsUS Department of Veterans Affairs [I01BX000545] Funding Source: NIH RePORTER Part of A. H.'s time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, Department of Veterans Affairs. |
| Databáze: | OpenAIRE |
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