Methylation of Tumor Suppressor Genes in Autoimmune Pancreatitis
Methylation of Tumor Suppressor Genes in Autoimmune Pancreatitis
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DOI：
10.1097/mpa.0000000000000804
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发表时间：
2017-05-01
期刊：
影响因子：
2.9
通讯作者：
Ota, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Kinugawa, Yasuhiro;Uehara, Takeshi;Ota, Hiroyoshi
目的：自身免疫性胰腺炎（AIP）是一种典型的IgG 4相关性炎症性疾病，病因不明。为了阐明AIP导致的致癌机制，我们重点关注AIP中的甲基化异常和KRAS突变。六个抑癌基因在10个AIP标本中选择在胰腺癌中表现出高甲基化的NPTX 2、Cyclin D2、FOXE 1、TFPI 2、ppENK和p16进行定量SYBR绿色甲基化特异性聚合酶链反应，10例无AIP病史的胰腺癌患者，包括癌区（CAs）和非癌区（NCAs），11例正常胰腺（NP）样本。结果：NPTX 2、Cyclin D2、FOXE 1、TFPI2、ppENK和p16分别有1、2、2、0、2和0例CA患者发生了>= 10%的高甲基化，而AIP、NCA和NP患者的这6个候选基因均未发生高甲基化。然而，AIP中TFPI2甲基化率显著高于NCA和NP。KRAS的直接测序结果显示AIP.Conclusions中没有单点突变：这些是表征AIP中甲基化异常的第一批研究。AIP的炎症状况可能与致癌作用有关。进一步的研究将阐明与AIP癌变相关的甲基化异常。
Objectives: Autoimmune pancreatitis (AIP) is a representative IgG4-related and inflammatory disease of unknown etiology. To clarify mechanisms of carcinogenesis resulting from AIP, we focused on methylation abnormalities and KRAS mutations in AIP.Methods: Six tumor suppressor genes (NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16) that exhibited hypermethylation in pancreatic carcinoma were selected for quantitative SYBR green methylation-specific polymerase chain reaction in 10 AIP specimens, 10 pancreatic adenocarcinoma cases without history of AIP containing carcinoma areas (CAs) and noncarcinoma areas (NCAs), and 11 normal pancreas (NP) samples. KRAS mutation in codons 12, 13, and 61 were also investigated using direct sequencing.Results: Hypermethylation events (>= 10%) were identified in NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16 in 1, 2, 2, 0, 2, and 0 CA cases, respectively, but not in these 6 candidate genes in AIP, NCA, and NP. However, the TFPI2 methylation ratio was significantly higher in AIP than NCA and NP. Direct sequencing results for KRAS showed no single-point mutations in AIP.Conclusions: These are the first studies characterizing methylation abnormalities in AIP. AIP's inflammatory condition may be related to carcinogenesis. Further study will elucidate methylation abnormalities associated with carcinogenesis in AIP.