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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 10/2020

01-10-2020 | Endoscopic Retrograde Pancreatography | Translational Research and Biomarkers

Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN)

Authors: Yoshiki Fujiyama, MD, Yusuke Kumamoto, MD, PhD, Nobuyuki Nishizawa, MD, PhD, Shuji Nakamoto, MD, Hiroki Harada, MD, Kazuko Yokota, MD, Yoko Tanaka, MD, Kazuharu Igarashi, MD, PhD, Hironobu Oiki, MD, Kosuke Okuwaki, MD, PhD, Tomohisa Iwai, MD, PhD, Sabine Kajita, MD, PhD, Hiroyuki Takahashi, MD, PhD, Hiroshi Tajima, MD, Takashi Kaizu, MD, PhD, Jiichiro Sasaki, MD, PhD, Masahiko Watanabe, MD, PhD, FACS, Keishi Yamashita, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 10/2020

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Abstract

Background

Intraductal papillary mucinous neoplasm (IPMN) involves adenoma (IPMA), a precancerous lesion, cancer (IPMC) including high-grade dysplasia (HGD), and invasive carcinoma (IC). DNA markers of IPMN are required for detection of invasive disease, and cysteine dioxygenase 1 (CDO1) gene promoter hypermethylation is a potential candidate. However, it has never been investigated in the context of IPMN.

Patients and Methods

A total of 107 IPMN tumor tissues, including 41 IPMC and 66 IPMA, were studied. CDO1 promoter methylation was quantified using TaqMan quantitative methylation-specific polymerase chain reaction (qMSP) in patients with IPMN and other pancreatic cystic disorders after pancreatectomy.

Results

The methylation values (TaqMeth Vs) of CDO1 increased when noncancerous pancreas tissues were compared with IPMA and HGD (p < 0.0001). Among IPMC, the TaqMeth Vs in IC were not significantly higher than in HGD. The TaqMeth Vs of the solid tumors were higher than those of the cystic tumors (p = 0.0016), which were in turn higher than the corresponding noncancerous tissues (p < 0.0001). Prognostic analysis revealed that high TaqMeth Vs (≥ 14.1) resulted in a poorer prognosis than low TaqMeth Vs (< 14.1) (p < 0.0001). In other pancreatic cystic diseases, only malignant mucinous cystic neoplasm showed DNA hypermethylation of its promoter. A pilot study in pancreatic juice confirmed methylation in all IPMN samples but not in benign pancreatic diseases (p = 0.0277).

Conclusions

CDO1 promoter hypermethylation is extremely specific to IPMN and may accumulate with IPMN tumor progression during the adenoma–carcinoma sequence. It might be a promising candidate as a diagnostic marker of pancreatic cystic diseases.
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Metadata
Title
Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN)
Authors
Yoshiki Fujiyama, MD
Yusuke Kumamoto, MD, PhD
Nobuyuki Nishizawa, MD, PhD
Shuji Nakamoto, MD
Hiroki Harada, MD
Kazuko Yokota, MD
Yoko Tanaka, MD
Kazuharu Igarashi, MD, PhD
Hironobu Oiki, MD
Kosuke Okuwaki, MD, PhD
Tomohisa Iwai, MD, PhD
Sabine Kajita, MD, PhD
Hiroyuki Takahashi, MD, PhD
Hiroshi Tajima, MD
Takashi Kaizu, MD, PhD
Jiichiro Sasaki, MD, PhD
Masahiko Watanabe, MD, PhD, FACS
Keishi Yamashita, MD, PhD, FACS
Publication date
01-10-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 10/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08291-2

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