Next-generation sequencing identifies 2 genomically distinct groups among pyloric gland adenomas

Namrata Setia*, Pankhuri Wanjari, Lindsay Yassan, Nifang Niu, Sabah Kadri, Lauren Ritterhouse, Joseph Misdraji, Ian Brown, Jeremy Segal, John Hart

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The molecular alterations identified among pyloric gland adenomas (PGAs) in the published literature are based on polymerase chain reaction of targeted genes, and next-generation sequencing (NGS) has not been performed. In this study, we performed NGS and correlated the molecular alterations with the histologic grade of dysplasia and immunohistochemical findings in a cohort of PGAs. Successful DNA extraction and sequencing were performed in 15 pyloric gland adenomas/adenocarcinoma from 12 patients. Additionally, 4 specimens of autoimmune gastritis were selected to serve as the control group. Ten PGAs with low-grade dysplasia were seen to have mutations in the triad of APC, KRAS, and GNAS genes. Five PGAs with high-grade dysplasia/adenocarcinoma exhibited mutations in several genes including APC, CTNNB1, KRAS, GNAS, TP53, CDKN2A, PIK3CA, and EPHA5 genes but did not exhibit mutations in the triad of APC, KRAS, and GNAS genes. The median tumor mutational burden was higher in PGAs with high-grade dysplasia/adenocarcinoma when compared with PGAs with low-grade dysplasia (5.25 and 4.38, respectively). PGAs with high-grade dysplasia/adenocarcinoma had more chromosomal gains and losses than PGAs with low-grade dysplasia. The molecular findings suggest that there are 2 separate mutator pathways of dysplasia development in PGAs.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalHuman pathology
Volume97
DOIs
StatePublished - Mar 2020

Keywords

  • Chromosomal alterations
  • Dysplasia
  • Genomic
  • Mutations
  • Next-generation sequencing
  • Pyloric gland adenoma
  • Sporadic

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Setia, N., Wanjari, P., Yassan, L., Niu, N., Kadri, S., Ritterhouse, L., Misdraji, J., Brown, I., Segal, J., & Hart, J. (2020). Next-generation sequencing identifies 2 genomically distinct groups among pyloric gland adenomas. Human pathology, 97, 103-111. https://doi.org/10.1016/j.humpath.2019.11.004