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

Autor: Go Asano, Katsuyuki Miyabe, Hiroyuki Kato, Michihiro Yoshida, Takeshi Sawada, Yasuyuki Okamoto, Hidenori Sahashi, Naoki Atsuta, Kenta Kachi, Akihisa Kato, Naruomi Jinno, Makoto Natsume, Yasuki Hori, Itaru Naitoh, Kazuki Hayashi, Yoichi Matsuo, Satoru Takahashi, Hiromu Suzuki, Hiromi Kataoka
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-021-04335-z
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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