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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Robin Imperial, Zaheer Ahmed, Omer M. Toor, Cihat Erdoğan, Ateeq Khaliq, Paul Case, James Case, Kevin Kennedy, Lee S. Cummings, Niklas Melton, Shahzad Raza, Banu Diri, Ramzi Mohammad, Bassel El-Rayes, Timothy Pluard, Arif Hussain, Janakiraman Subramanian, Ashiq Masood

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. More... »

PAGES

177

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12943-018-0923-9

DOI

http://dx.doi.org/10.1186/s12943-018-0923-9

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https://app.dimensions.ai/details/publication/pub.1110824940

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30577807


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