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. 2020 Oct;27(10):4007-4016.
doi: 10.1245/s10434-020-08291-2. Epub 2020 Mar 6.

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

Yoshiki Fujiyama  1 , Yusuke Kumamoto  1 , Nobuyuki Nishizawa  1 , Shuji Nakamoto  1 , Hiroki Harada  1 , Kazuko Yokota  1 , Yoko Tanaka  1 , Kazuharu Igarashi  1 , Hironobu Oiki  1 , Kosuke Okuwaki  2 , Tomohisa Iwai  2 , Sabine Kajita  3 , Hiroyuki Takahashi  3 , Hiroshi Tajima  1 , Takashi Kaizu  1 , Jiichiro Sasaki  4 , Masahiko Watanabe  1 , Keishi Yamashita  5   6
Affiliations

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

Yoshiki Fujiyama et al. Ann Surg Oncol. 2020 Oct.

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.

Keywords: CDO1; IPMN; Methylation.

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