To interrogate the implications of the DDR gene aberrations underlying GIST pathogenesis and progression, we performed targeted next-generation sequencing (NGS), analyzed the expression status and clinicopathologic associations of γ-H2AX and 53BP1 using whole-tissue blocks and tissue microarrays (TMAs), and employed multiplex ligation-dependent probe amplification (MLPA) assays to profile CNVs of BRCA2, CHEK2, and RB1 in GISTs, to derive correlation with immunohistochemistry (IHC) and immunofluorescence (IF) results for γ-H2AX and 53BP1. The gene discussed is H2AX; the disease is gastrointestinal stromal tumor.