Abstract

Epigenetics of Solid Pseudopapillary Neoplasm of the Pancreas

Background The solid pseudopapillary neoplasm of pancreas is a rare neoplasm with low-grade malignancy and uncertain origin that constitutes about 1-2% of all exocrine pancreatic neoplasms. Epigenetic events such as deoxyribonucleic acid methylation lead to altered gene expression, resulting in altered control of cell proliferation. Based on the fact that epigenetic changes are reversible, the importance of epigenetic studies lies in the better understanding of tumor progression as well as target therapy. Objective This study had the objective to evaluate the intratumor heterogeneity of solid pseudopapillary neoplasm of pancreas in three macroscopically distinct areas, comparing gene polymorphism and gene methylation. Material and Methods The samples were collected from three distinct tumor areas from one female patient diagnosed with Solid pseudopapillary neoplasm of pancreas and submitted to a pancreatectomy. Deoxyribonucleic acid was extracted from the fresh tissues by using proteinase K digestion and phenol-chloroform isoamyl alcohol followed by ethanol precipitation. The functionality of deoxyribonucleic acid was investigated for GSTT1 (glutathione S-transferase theta 1) and GSTM1 (glutathione S-transferase mu 1) genes by multiplex polymerase chain reaction. Methylation-specific polymerase chain reaction analysis was used to determine the methylation status of: p16, RB1, E-cadherin, TIMP2 and DAPK genes promoter by bisulfite modification. Results and Conclusion The results show a null genotype for GSTT1 in tumor areas 1 and 3 when comparing with area 2, showing that there is heterogeneity in the tumor. Tumor fragment 1 was not detected for any investigated genes in methylation, probably due to deoxyribonucleic acid degradation in this region. TIMP-2 (tissue metallopeptidase inhibitor 2) and p16 were methylated in areas 2 and 3, and E-cadherin presented a small methylation only in fragment 3; DAPK and RB1 (retinoblastoma 1) were unmethylated. As far as we know, this is the first work to show deoxyribonucleic acid methylation in solid pseudopapillary neoplasm of pancreas.


Author(s): Vera Lucia Antunes Chagas, Bruna dos Santos Paiva Ribeiro, Marcelo Soares da Mota e Silva, Danielle Nunes Forny, Fernando Colonna Rosman, Maria da Gloria da Costa Carvalho

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