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Clinical prognostic value of DNA methylation in hepatoblastoma : Four novel tumor suppressor candidates

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Title: Clinical prognostic value of DNA methylation in hepatoblastoma : Four novel tumor suppressor candidates
Authors: Honda, Shohei Browse this author →KAKEN DB
Minato, Masashi Browse this author
Suzuki, Hiromu Browse this author →KAKEN DB
Fujiyoshi, Masato Browse this author
Miyagi, Hisayuki Browse this author
Haruta, Masayuki Browse this author →KAKEN DB
Kaneko, Yasuhiko Browse this author →KAKEN DB
Hatanaka, Kanako C. Browse this author
Hiyama, Eiso Browse this author →KAKEN DB
Kamijo, Takehiko Browse this author
Okada, Tadao Browse this author
Taketomi, Akinobu Browse this author →KAKEN DB
Keywords: Hepatoblastoma
methylation
prognostic marker
survival
tumor suppressor
Issue Date: Jun-2016
Publisher: Japanese Cancer Association
Journal Title: Cancer science
Volume: 107
Issue: 6
Start Page: 812
End Page: 819
Publisher DOI: 10.1111/cas.12928
Abstract: Hepatoblastoma (HB) is very rare but the most common malignant neoplasm of the liver occurring in children. Despite improvements in therapy, outcomes for patients with advanced HB that is refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the survival rate among this group, identification of novel prognostic markers and therapeutic targets is needed. We have previously reported that altered DNA methylation patterns are of biological and clinical importance in HB. In the present study, using genome-wide methylation analysis and bisulfite pyrosequencing with specimens from HB tumors, we detected nine methylated genes. We then focused on four of those genes, GPR180, MST1R, OCIAD2, and PARP6, because they likely encode tumor suppressors and their increase of methylation was associated with a poor prognosis. The methylation status of the four genes was also associated with age at diagnosis, and significant association with the presence of metastatic tumors was seen in three of the four genes. Multivariate analysis revealed that the presence of metastatic tumors and increase of methylation of GPR180 were independent prognostic factors affecting event-free survival. These findings indicate that the four novel tumor suppressor candidates are potentially useful molecular markers predictive of a poor outcome in HB patients, which may serve as the basis for improved therapeutic strategies when clinical trials are carried out.
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article
URI: http://hdl.handle.net/2115/62711
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 本多 昌平

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