Conclusions:

This is the largest and most extensive profiling study to investigate the molecular makeup of IDH1/2 mutated BC and GI tumors. • IDH1/2 mutations are more prevalent in IHCC compared to other BC. • IDH1/2 mutations are more prevalent in BC compared to other GI malignancies. • Our data show distinct gene alteration patterns characterizing mIDH BC, involving genes related to chromatin remodeling and DNA repair, and a differential expression of immune related markers compared to other mIDH GI tumors. • These findings could contribute to the development of rational combination therapies and to improved patient selection in the future.