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NRAS mutant E132K identified in young-onset sporadic colorectal cancer and the canonical mutants G12D and Q61K affect distinct oncogenic phenotypes.

Author

Ryan Timothy  D. Yu,
Reynaldo  L. Garcia

Related Institution

Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology - University of the Philippines Diliman

OVPAA-EIDR - University of the Philippines System

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Publication Information

Publication Type
Journal
Publication Sub Type
Journal Article, Original
Project Title
Functional Characterization of Novel Mutations in Downstream Effectors of the EGFR Signaling Pathway among Filipino Colorectal Cancer Patients
Title
Scientific Reports
Frequency
Others
Publication Date
2020
Volume
10
Issue
NA
Page(s)
NA

Abstract

Recent data show a global increase in colorectal cancer (CRC) cases among younger demographics, which portends poorer prognosis. The cause of rising incidence is uncertain, and its mutational landscape remains largely unexplored, including those in genes of the epidermal growth factor receptor pathway. Among these are NRAS mutants where there is paucity of functional studies compared to KRAS. Here, the novel NRAS mutant E132K, identified in three tumor samples from Filipino young-onset, sporadic colorectal cancer patients, was investigated for its effects on different cancer hallmarks, alongside the NRAS canonical mutants G12D and Q61K which are yet poorly characterized in the context of CRC. The novel NRAS mutant E132K and the canonical G12D and Q61K mutants show resistance to apoptosis, cytoskeletal reorganization, and loss of adhesion. In contrast to activating KRAS mutations, including the analogous KRAS G12D and Q61K mutations, all three NRAS mutants have no apparent effect on cell proliferation and motility. The results highlight the need to characterize isoform- and mutation-specific oncogenic phenotypes which can have repercussions in disease management and choice of therapeutic intervention. Further analyses of young-onset versus late-onset CRC datasets are necessary to qualify NRAS E132K as a biomarker for the young-onset subtype.

References

1. Kaw, L. L., , Punzalan, C. K, , Crisostomo, A. C., , Bowyer, M. W., , Wherry, D. C., . "Surgical pathology of colorectal cancer in Filipinos: implications for clinical practice" Journal of the American College of Surgeons 195, 188–195, 2002

Physical Location

LocationLocation CodeAvailable FormatAvailability
Philippine Council for Health Research and Development Fulltext pdf (Request Document)
Nature Publishing Group Fulltext External Link (View)

 
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