Relevance of gene mutations and methylation to the growth of pancreatic intraductal papillary mucinous neoplasms based on pyrosequencing.

Relevance of gene mutations and methylation to the growth of pancreatic intraductal papillary mucinous neoplasms based on pyrosequencing.
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DOI:
10.1038/s41598-021-04335-z
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发表时间:
2022-01-10
期刊:
影响因子:
4.6
通讯作者:
Kataoka H
Kataoka H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Asano G;Miyabe K;Kato H;Yoshida M;Sawada T;Okamoto Y;Sahashi H;Atsuta N;Kachi K;Kato A;Jinno N;Natsume M;Hori Y;Naitoh I;Hayashi K;Matsuo Y;Takahashi S;Suzuki H;Kataoka H

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我们的目的是通过评估基因突变和甲基化来评估非恶性导管内乳头状黏液性肿瘤(IPMN)发生癌症的一些潜在遗传途径。总共分析了33例IPMN病例的46个解剖区域,并在恶性潜在病例和良性病例之间,或在恶性潜在组织解剖区域和良性组织解剖区域之间进行了比较,包括伴有恶性潜在区域的低度IPMN解剖区域。通过焦磷酸测序和免疫组织化学分析评估了几种基因突变、基因甲基化和蛋白质。RASSF 1A甲基化在潜在恶性切割区域中更常见(p = 0.0329)。LINE-1甲基化与GNAS突变呈负相关(r =-0.3739,p = 0.0105)。与无GNAS突变的潜在恶性肿瘤病例相比,在存在潜在恶性肿瘤切除区域的病例中,GNAS突变与较低频率的血管周围浸润(p = 0.0128)、神经周围浸润(p = 0.0377)和淋巴结转移(p = 0.0377)相关,但总生存率显著延长(p = 0.0419)。在分支导管IPMN病例中,潜在恶性和良性解剖区域中一致的KRAS和GNAS突变的存在比其他类型更常见(p = 0.0319)。RASSF 1A、CDKN 2A、LINE-1甲基化及GNAS突变可能与肿瘤发生、IPMN亚型及预后有关。
We aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions (p = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation (r =  − 0.3739, p = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion (p = 0.0128), perineural invasion (p = 0.0377), and lymph node metastasis (p = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation (p = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types (p = 0.0319). Methylation of RASSF1A, CDKN2A, and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.
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