Journal article
Next-generation sequencing identifies 2 genomically distinct groups among pyloric gland adenomas
Human pathology, Vol.97, pp.103-111
03/2020
DOI: 10.1016/j.humpath.2019.11.004
PMID: 31783043
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.
•Next-generation sequencing of pyloric gland adenomas (PGAs) identified two distinct genomic groups.•PGAs with mutations in the triad of APC, KRAS and GNAS genes corresponded to morphologic low-grade dysplasia.•PGAs with high-grade dysplasia/adenocarcinoma had a diverse mutational profile and frequent chromosomal alterations.
Details
- Title: Subtitle
- Next-generation sequencing identifies 2 genomically distinct groups among pyloric gland adenomas
- Creators
- Namrata Setia - University of ChicagoPankhuri Wanjari - University of ChicagoLindsay Yassan - Rush UniversityNifang Niu - University of ChicagoSabah Kadri - Northwestern UniversityLauren Ritterhouse - Harvard UniversityJoseph Misdraji - Harvard UniversityIan Brown - Envoi Specialist PathologistsJeremy Segal - University of ChicagoJohn Hart - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Human pathology, Vol.97, pp.103-111
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.humpath.2019.11.004
- PMID
- 31783043
- ISSN
- 0046-8177
- eISSN
- 1532-8392
- Number of pages
- 9
- Grant note
- Department of Pathology, University of Chicago
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984701557402771
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