Provided herein are methods related to detecting rearrangements in the B-cell lymphoma 6 (BCL6) corepressor (BCOR) or BCL6 corepressor-like protein I (BCORL1) gene, as well as methods of treatment, uses, and kits related thereto. As demonstrated herein, detection of BCOR rearrangements can be used to identify individuals that may benefit from treatment with a targeted therapeutic, such as a CDK inhibitor, an MDM2 inhibitor, a tyrosine kinase inhibitor, a MEK inhibitor, an mTOR inhibitor, or a Hh inhibitor. In some embodiments, the BCOR rearrangement is a fusion gene between BCOR and L3MBTL2, EP300, NUTM2G, MAP7D2, RALGPS1 RGAG1, CREBBP, ING3, NUGGC, or KMT 2D.