Abstract：
BACKGROUND: Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remains unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported.
METHODS: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes.
RESULTS: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs.
CONCLUSIONS: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.
METHODS: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes.
RESULTS: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs.
CONCLUSIONS: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.
摘要：
背景：腹膜假粘液瘤（PMP）是一种疾病，其特征是由腹腔肿瘤产生的腹膜内粘液性腹水的进行性积累。由于PMP患者的预后仍然不令人满意，开发有效的治疗药物是一个紧迫的问题。PMP的遗传分析已经阐明了GNAS和/或KRAS的频繁激活。然而,PMPs涉及全球表观遗传改变的报道尚未出现.
方法：为了阐明15个PMP肿瘤的遗传背景，我们使用AmpliSeq癌症热点面板v2进行了遗传分析。我们使用包含总共865,918个探针的甲基化EPIC阵列BeadChip（Infinium850k）进一步研究了15种肿瘤和8种非癌性结肠上皮细胞中的全局DNA甲基化。
结果：这是世界上有关PMPs的全面DNA甲基化谱的第一份报告。我们澄清了15个PMPs可以分为至少两种表观基因型，独特的甲基化表观基因型（UME）和正常样甲基化表观基因型（NLME），与神经元发育和突触信号相关的基因可能参与了PMPs的发育。此外,我们在15个PMPs中鉴定了一组高甲基化标记基因如HOXD1和TSPYL5。
结论：这些发现可能有助于了解PMP的分子机制，并有助于开发这种危及生命的疾病的治疗策略。
方法：为了阐明15个PMP肿瘤的遗传背景，我们使用AmpliSeq癌症热点面板v2进行了遗传分析。我们使用包含总共865,918个探针的甲基化EPIC阵列BeadChip（Infinium850k）进一步研究了15种肿瘤和8种非癌性结肠上皮细胞中的全局DNA甲基化。
结果：这是世界上有关PMPs的全面DNA甲基化谱的第一份报告。我们澄清了15个PMPs可以分为至少两种表观基因型，独特的甲基化表观基因型（UME）和正常样甲基化表观基因型（NLME），与神经元发育和突触信号相关的基因可能参与了PMPs的发育。此外,我们在15个PMPs中鉴定了一组高甲基化标记基因如HOXD1和TSPYL5。
结论：这些发现可能有助于了解PMP的分子机制，并有助于开发这种危及生命的疾病的治疗策略。
