Sebastiao APM, et al. - Via four polymorphous adenocarcinoma (PACs) from three patients with high-grade histology, the researchers intended to ascertain the genetic underpinning of recurrent PACs of the salivary gland and the repertoire of somatic genetic alterations. Clonal PRKD1 E710D hotspot mutations were harbored by both matching primary and recurrent tumors and the de-novo high-grade PAC, while PRKD2 rearrangement was harbored by the PAC that was wild-type for PRKD1 which underwent high-grade transformation upon recurrence. Further, following a clonal selection evolutionary pattern, a minor subclone from the primary tumor was observed becoming dominant in the recurrent tumor. Hence, it was exhibited that recurrent and high-grade PACs were underpinned by PRKD1 E710D hotspot mutations or PRKD2 rearrangements. Also, from the selection of pre-existing subclones in the primary tumor, recurrences of PACs could be originated.