Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors

ABSTRACT: ROS1 is the largest receptor tyrosine kinase in the human genome. Rearrangements of the ROS1 gene result in oncogenic ROS1 kinase fusion proteins that are currently the only validated biomarkers for targeted therapy with ROS1 TKIs in patients. While numerous somatic missense mutations in ROS1 exist in the cancer genome, their impact on catalytic activity and pathogenic potential is unknown. We interrogated the AACR Genie database and identified thirty-four missense mutations in the ROS1 tyrosine kinase domain for further analysis. Our experiments revealed that these mutations have varying effects on ROS1 kinase function, ranging from complete loss to significantly increased catalytic activity. Notably, Asn and Gly substitutions at Asp2113 in the ROS1 kinase domain were found to be TKI-sens

SUBMITTER: Mr. Sudarshan, R Iyer 

PROVIDER: S-SCDT-10_15252-EMMM_202217367 | biostudies-other |

REPOSITORIES: biostudies-other