Here, in order to identify rare tumor‐related genomic alterations for further functional validation and therapeutic targeting studies, we applied whole genome sequencing (WGS) on a pair of MZ twins discordant for lung inflammatory myofibroblastoma (IMT), a rare mesenchymal neoplasm that accounts for <1% of lung neoplasms.[23, 24, 25] Genetic screening and functional studies of candidate mutations led to a single nucleotide variation of lysine methyltransferase SETD8 (SETD8C302R) that resulted in dysfunctional p53/p21 pathway and increased sensitivity to WEE1 inhibition. The gene discussed is KMT5A; the disease is neoplasm.