Pancreatoblastomas and mixed and pure acinar cell carcinomas share epigenetic signatures distinct from other neoplasms of the pancreas Journal Article
| Authors: | Benhamida, J. K.; Vyas, M.; Tanaka, A.; Wang, L.; Bahrami, A.; Ozcan, K.; Basturk, O.; Villafania, L.; Mata, D. A.; El Jabbour, T.; Selenica, P.; Roehrl, M. H. A.; Weigelt, B.; Reis-Filho, J. S.; Scaltriti, M.; Klimstra, D. S. |
| Article Title: | Pancreatoblastomas and mixed and pure acinar cell carcinomas share epigenetic signatures distinct from other neoplasms of the pancreas |
| Abstract: | Pancreatic neoplasms are heterogenous and have traditionally been classified by assessing their lines of cellular differentiation using histopathologic methods, particularly morphologic and immunohistochemical evaluation. These methods frequently identify overlapping differentiation along ductal, acinar, and neuroendocrine lines, raising diagnostic challenges as well as questions regarding the relationship of these neoplasms. Neoplasms with acinar differentiation, in particular, frequently show more than one line of differentiation based on immunolabeling. Genome methylation signatures, in contrast, are better conserved within cellular lineages, and are increasingly used to support the classification of neoplasms. We characterized the epigenetic relationships between pancreatoblastomas, acinar cell carcinomas (including mixed variants), pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, and pancreatic ductal adenocarcinomas using a genome-wide array platform. Using unsupervised learning approaches, pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, ductal adenocarcinomas, and normal pancreatic tissue samples all localized to distinct clusters based on their methylation profiles, whereas all neoplasms with acinar differentiation occupied a broad overlapping region located between the predominantly acinar normal pancreatic tissue and ductal adenocarcinoma clusters. Our data provide evidence to suggest that acinar cell carcinomas and pancreatoblastomas are similar at the epigenetic level. These findings are consistent with genomic and clinical observations that mixed acinar neoplasms are closely related to pure acinar cell carcinomas rather than to neuroendocrine tumors or ductal adenocarcinomas. © 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Keywords: | controlled study; human tissue; major clinical study; genetics; pancreatic neoplasms; pancreas; metabolism; cell differentiation; pathology; dna methylation; epigenetics; epigenesis, genetic; pancreas tumor; genome; acinar cell carcinoma; carcinoma, acinar cell; false positive result; genetic epigenesis; neuroendocrine carcinoma; pancreas islet cell tumor; solid pseudopapillary tumor; pancreatic ductal carcinoma; dimensionality reduction; foam cell; humans; human; article; hierarchical clustering; pancreas tissue |
| Journal Title: | Modern Pathology |
| Volume: | 35 |
| Issue: | 7 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2022-07-01 |
| Start Page: | 956 |
| End Page: | 961 |
| Language: | English |
| DOI: | 10.1038/s41379-021-00989-2 |
| PUBMED: | 34969956 |
| PROVIDER: | scopus |
| PMCID: | PMC10319432 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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