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- Genomic analysis of recurrences and high-grade forms of polymorphous adenocarcinomas.
- Paper ID
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
PMID: 30843621 (view at PubMed or Europe PMC)
- Aim: Polymorphous adenocarcinoma (PAC) usually follows an indolent course, but some cases may display recurrences and high-grade features. The genetic events associated with recurrences and high-grade versions are yet to be defined. Our aim was to determine the genetic underpinning of recurrent PACs of the salivary gland and the repertoire of somatic genetic alterations in cases with high-grade histology.Four PACs from three patients, including one case with matching primary and recurrent tumors, one de novo high-grade PAC, and a PAC that transformed to a high-grade tumor following multiple recurrences, were subjected to targeted (MSK-IMPACT) or whole-exome sequencing (WES). Both matching primary and recurrent tumor as well as the de novo high grade PAC harbored clonal PRKD1 E710D hotspot mutations, whereas the PAC that underwent high-grade transformation upon recurrence, which was wild-type for PRKD1, harbored a PRKD2 rearrangement. The PACs analyzed here also harbored mutations targeting cancer genes such as PIK3CA, SETD2, ARID1A and NOTCH2. A clonal decomposition analysis of the matching primary and recurrent PACs revealed that a minor sub-clone from the primary tumor became dominant in the recurrent tumor following a clonal selection evolutionary pattern.Conclusions: Our findings demonstrate that recurrent and high-grade PACs are underpinned by PRKD1 E710D hotspot mutations or PRKD2 rearrangements, and that recurrences of PACs may stem from the selection of preexisting sub-clones in the primary tumor. This article is protected by copyright. All rights reserved.
- Paper Status