AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common intra-oral salivary gland malignancy. The vast majority of PLGAs harbour a PRKD1 E710D hot-spot somatic mutation or somatic rearrangements of PRKD1, PRKD2 or PRKD3. Given the kinase domain homology among PRKD1, PRKD2 and PRKD3, we sought to define whether PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements would be driven by somatic mutations affecting the kinase domains of PRKD2 or PRKD3. METHODS AND RESULTS: DNA was extracted from eight microdissected PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements. Samples were thoroughly centrally reviewed, microdissected and subjected to Sanger sequencing of the kinase domains of the PRKD2 and PRKD3 genes. None of the PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements harboured somatic mutations in the kinase domains of the PRKD2 or PRKD3 genes. CONCLUSION: PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements are unlikely to harbour somatic mutations in the kinase domains of PRKD2 or PRKD3. Further studies are warranted to define the driver genetic events in this subgroup of PLGAs.

• MeSH
• Adenocarcinoma diagnosis   enzymology   genetics   pathology   MeSH
• Adult MeSH
• Genotype MeSH
• Gene Rearrangement MeSH
• Middle Aged MeSH
• Humans MeSH
• Microdissection MeSH
• Mutation MeSH
• Salivary Gland Neoplasms diagnosis   enzymology   genetics   pathology   MeSH
• Protein Kinase C genetics   MeSH
• Protein Domains MeSH
• Amino Acid Sequence MeSH
• Sequence Analysis, DNA MeSH
• Sequence Alignment MeSH
• Aged MeSH
• Salivary Glands pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

• MeSH
• Adenocarcinoma genetics   pathology   MeSH
• NIH 3T3 Cells MeSH
• Immunohistochemistry MeSH
• Immunoprecipitation MeSH
• Microscopy, Confocal MeSH
• Humans MeSH
• Mutation, Missense genetics   MeSH
• Models, Molecular * MeSH
• Molecular Sequence Data MeSH
• Mutagenesis MeSH
• Mice MeSH
• Salivary Gland Neoplasms genetics   pathology   MeSH
• Protein Kinase C chemistry   genetics   MeSH
• Amino Acid Sequence MeSH
• Sequence Analysis, DNA MeSH
• Sequence Alignment MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH