Comprehensive genomic and epigenetic analysis of ESCC to construct new therapeutic modality

2014 Fiscal Year Final Research Report

• Project/Area Number: 24300341
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAWANO Tatsuyuki 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (00186115)
• Co-Investigator(Kenkyū-buntansha): INAZAWA Johji 東京医科歯科大学, 難治疾患研究所, 教授 (30193551) ; EISHI Yoshinobu 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (70151959) ; OMURA Ken 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (10334434)
• Co-Investigator(Renkei-kenkyūsha): KOZAKI Ken-ichi 東京医科歯科大学, 難治疾患研究所, 准教授 (50270715)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 食道扁平上皮癌 / ゲノム解析 / エピゲノム解析 / マイクロRNA / 全エクソンシーケンス / Field cancerization / heterogeneity

Outline of Final Research Achievements

Esophageal squamous cell carcinoma (ESCC) is one of the cancers with poor prognosis, and there are no effective molecular targeted drugs to ESCC yet. To clarify valuable biomarkers or therapeutic targets, we analyzed ESCC clinical samples mainly using a technique of genomic or epigenetic analysis. Whole-exome sequencing revealed some common mutations between two distinct tumors in the same patient, which might explain the mechanism of field cancerization. A comprehensive analysis of methylation status revealed several differentially methylated regions (DMRs) which relate to lymph node metastasis. This might be a novel diagnostic tool to predict lymph node metastasis in ESCC patients. Moreover, we identified tumor-suppressor microRNA which expression was often down-regulated in ESCC clinical samples. This microRNA might be a novel therapeutic agent in ESCC. Though it requires further investigations, we expect that these findings contribute to improve the prognosis of ESCC patients.

Free Research Field

食道外科