<i>RAS</i> internal tandem duplication disrupts GTPase-activating protein (GAP) binding to activate oncogenic signaling.

ABSTRACT: The oncogene RAS is one of the most widely studied proteins in cancer biology, and mutant active RAS is a driver in many types of solid tumors and hematological malignancies. Yet the biological effects of different RAS mutations and the tissue-specific clinical implications are complex and nuanced. Here, we identified an internal tandem duplication (ITD) in the switch II domain of NRAS from a patient with extremely aggressive colorectal carcinoma. Results of whole-exome DNA sequencing of primary and metastatic tumors indicated that this mutation was present in all analyzed metastases and excluded the presence of any other clear oncogenic driver mutations. Biochemical analysis revealed increased interaction of the RAS ITD with Raf proto-oncogene Ser/Thr kinase (RAF), leading to incre

SUBMITTER: Nelson AC 

PROVIDER: S-EPMC7363148 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature