Notably, we find recurrent ADGRG6 enhancer mutations and FRS2 duplications which are associated with higher protein expression in the tumor and poor prognosis.
Lenvatinib inhibited in vivo tumor growth in Hep3B2.1-7 and SNU-398 xenografts and decreased phosphorylation of FRS2 and Erk1/2 within the tumor tissues.
These findings suggest that FRS2 is amplified consistently in ALT/WDL/DDLs and offer another avenue for the investigation of the biology of this tumour group.
We found that FRS2-amplified cancer cell lines are dependent on FRS2 expression, and that FRS2 overexpression in immortalized human cell lines conferred the ability to grow in an anchorage-independent manner and as tumors in immunodeficient mice.
MDM2 and FRS2 play important roles as a regulator of p53 and a mediator of FGF signaling, respectively, and thus are potential molecular targets for therapy in many different tumors.