Genomic analysis of recurrences and high-grade forms of polymorphous adenocarcinoma Journal Article


Authors: Sebastiao, A. P. M.; Pareja, F.; Kumar, R.; Brown, D. N.; Silveira, C.; da Silva, E. M.; Lee, J. Y.; Del, A.; Katabi, N.; Chiosea, S.; Weigelt, B.; Reis-Filho, J. S.; Seethala, R. R.
Article Title: Genomic analysis of recurrences and high-grade forms of polymorphous adenocarcinoma
Abstract: Aims: Polymorphous adenocarcinoma (PAC) usually follows an indolent course, but some cases may show 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. Methods and results: Four PACs from three patients, including one case with matching primary and recurrent tumours, one de-novo high-grade PAC, and a PAC that transformed to a high-grade tumour following multiple recurrences, were subjected to targeted sequencing (Memorial Sloan Kettering Mutation Profiling of Actionable Cancer Targets assay) or whole-exome sequencing. Both matching primary and recurrent tumours, and the de-novo high-grade PAC, harboured clonal PRKD1 E710D hotspot mutations, whereas the PAC that underwent high-grade transformation upon recurrence, which was wild-type for PRKD1, harboured a PRKD2 rearrangement. The PACs analysed here also harboured 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 subclone from the primary tumour became dominant in the recurrent tumour 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 pre-existing subclones in the primary tumour. © 2019 John Wiley & Sons Ltd
Keywords: next-generation sequencing; whole-exome sequencing; polymorphous adenocarcinoma; prkd1; prkd2; prkd3
Journal Title: Histopathology
Volume: 75
Issue: 2
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2019-08-01
Start Page: 193
End Page: 201
Language: English
DOI: 10.1111/his.13854
PUBMED: 30843621
PROVIDER: scopus
PMCID: PMC7920221
DOI/URL:
Notes: Article -- Export Date: 2 August 2019 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Nora Katabi
    239 Katabi
  2. Britta Weigelt
    409 Weigelt
  3. Jorge Sergio Reis
    457 Reis
  4. Rahul Kumar
    23 Kumar
  5. Ju Youn Lee
    13 Lee
  6. David Norman Brown
    50 Brown
  7. Angela Del
    2 Del