Epigenetics of Solid Pseudopapillary Neoplasm of the Pancreas
Epigenetics of Solid Pseudopapillary Neoplasm of the Pancreas
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胰腺实性假乳头状肿瘤的表观遗传学
DOI：
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发表时间：
2018
期刊：
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通讯作者：
M. Carvalho
中科院分区：
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作者：
V. Chagas;B. Ribeiro;M. Silva;D. N. Forny;Fern;O. C. Rosman;M. Carvalho
胰腺实性假乳头状肿瘤是一种罕见的肿瘤，恶性程度低，起源不明，约占胰腺外分泌肿瘤的1-2%。表观遗传事件，如脱氧核糖核酸甲基化，导致改变基因表达，从而改变细胞增殖的控制。基于表观遗传学改变是可逆的这一事实，表观遗传学研究的重要性在于更好地理解肿瘤进展以及靶向治疗。目的比较胰腺实性假乳头状瘤的基因多态性和基因甲基化情况，探讨胰腺实性假乳头状瘤的异质性。材料与方法1例胰腺实性假乳头状瘤女性患者，从3个不同的肿瘤区域收集标本，并进行胰腺切除术。新鲜组织经蛋白酶K消化、酚-氯仿异戊醇沉淀、乙醇沉淀后提取脱氧核糖核酸。通过多重聚合酶链反应研究了GSTT 1（谷胱甘肽S-转移酶θ 1）和GSTM 1（谷胱甘肽S-转移酶μ 1）基因的脱氧核糖核酸功能。采用甲基化特异性聚合酶链反应（PCR）检测p16、RB 1、E-cadherin、TIMP 2和DAPK基因启动子甲基化状态。结果与结论GSTT 1基因在肿瘤1区和3区均为零基因型，与肿瘤2区相比，肿瘤存在异质性。对于任何研究的甲基化基因，均未检测到肿瘤片段1，可能是由于该区域的脱氧核糖核酸降解。TIMP-2（组织金属肽酶抑制剂2）和p16在区域2和3中甲基化，E-钙粘蛋白仅在片段3中呈现小的甲基化; DAPK和RB 1（视网膜母细胞瘤1）未甲基化。据我们所知，这是第一次在胰腺实性假乳头状瘤中发现脱氧核糖核酸甲基化。
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.