Global analysis of genomic alterations associated with AKT and ERK pathway in esophageal squamous cell carcinoma

• Project/Area Number: 23591941
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: MIYANARI Nobutomo 熊本大学, 医学部附属病院, 非常勤診療医師 (90336230)
• Co-Investigator(Kenkyū-buntansha): BABA Hideo 熊本大学, 大学院生命科学研究部, 教授 (20240905) ; BABA Yoshifumi 熊本大学, 大学院生命科学研究部, 講師 (20599708) ; IWATSUKI Masaaki 熊本大学, 医学部附属病院, 非常勤診療医師 (50452777)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: genomic alteration / 食道扁平上皮癌 / KRAS / BRAF / PIK3CA / 遺伝子変異 / 同時性肝転移 / 食道癌 / 予後 / pyrosequence

Research Abstract

Using resected ESCC specimens,we investigate mutations of KRAS,BRAF and PIK3CA by Pyrosequencing technology.As a result,the KRAS mutation was found to be extremely rare(1 of 203;0.5%),and the BRAF mutation was absent(0 of 203;0%),suggesting that KRAS and BRAF mutations play a limited role in the development of ESCC.However,PIK3CA mutations mutations in ESCC are associated with longer overall survival and cancer-specific survival,suggesting its role as a prognostic biomarker.We evaluated colorectal cancer with synchronous liver metastases. We evaluated KRAS,BRAF,and PIK3CA mutation status and microsatellite instability(MSI) status in 42 liver metastases, 26 matched primary tumors, and 6 matched lymph node(LN) metastases by Pyrosequencing technology.We also quantified LINE-1 methylation levels.The concordance rate was 94% for KRAS,100% for BRAF,88% for PIK3CA,and 97% for MSI.Primary tumors showed LINE-1 methylation levels similar to those of matched liver and LN metastases.

Research Products

• [Journal Article] PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma (2013)
  • Author(s): Shigaki H, Baba Y, Watanabe M, Murata A, Ishimoto T, Iwatsuki M, Iwagami S, Nosho K, Baba H.
  • Journal Title: Clin Cancer Res. Volume: 19(9) Issue: 9 Pages: 2451-9
  • DOI: 10.1158/1078-0432.ccr-12-3559
  • Peer Reviewed
• [Journal Article] KRAS and BRAF Mutations in 203 Esophageal Squamous Cell Carcinomas : Pyrosequencing Technology and Literature Review (2013)
  • Author(s): Shigaki H, Baba Y, Watanabe M, Miyake K, Murata A, Iwagami S, Ishimoto T, Iwatsuki M, Yoshida N, Baba H.
  • Journal Title: Ann Surg Oncol Volume: 20(3) Issue: S3 Pages: 485-91
  • DOI: 10.1245/s10434-012-2819-z
  • Peer Reviewed
• [Journal Article] Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer. (2013)
  • Author(s): Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Iwagami S, Sakamoto Y, Miyamoto Y, Yoshida N, Nosho K, Baba H.
  • Journal Title: Br J Cancer. Volume: 109 Issue: 2 Pages: 408-415
  • DOI: 10.1038/bjc.2013.289
  • Peer Reviewed
• [Journal Article] PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. (2013)
  • Author(s): Shigaki H, Baba Y et al.
  • Journal Title: Clin Cancer Res. Volume: In press
  • Peer Reviewed
• [Journal Article] KRAS and BRAF Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review. (2013)
  • Author(s): Shigaki H, Baba Y et al.
  • Journal Title: Ann Surg Oncol. Volume: In press
  • Peer Reviewed
• [Journal Article] Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 (2012)
  • Author(s): Kurashige J , Watanabe M , Iwatsuki M , Kinoshita K , Saito S , Hiyoshi Y , Kamohara H , Baba H , Mimori K
  • Journal Title: British Journal of Cancer Volume: 106 Pages: 182-188
  • Peer Reviewed
• [Journal Article] Carcinogenesis of Intraductal Papillary Mucinous Neoplasm of the Pancreas: Loss of MicroRNA-101 Promotes Overexpression of Histone Methyltransferase EZH2 (2012)
  • Author(s): Nakahara O , Takamori H , Iwatsuki M , Baba Y , Sakamoto Y , Tanaka H , Chikamoto A , Horino K , Beppu T , Kanemitsu K , Honda Y , Iyama K , Baba H
  • Journal Title: Ann Surg Oncol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] MicroRNA-200b regulates cell proliferation, invasion and migration by directly targeting ZEB2 in gastric carcinoma (2012)
  • Author(s): Kurashige J , Kamohara H , Watanabe M , Hiyoshi Y , Iwatsuki M , Tanaka Y , Kinoshita K , Saito S , Baba Y , Baba H
  • Journal Title: Annals of Surgical Oncology Epub ahead of print Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma (2012)
  • Author(s): Kurashige J , Kamohara H , Watanabe M , Tanaka Y , Kinoshita K , Saito S , Hiyoshi Y , Iwatsuki M , Baba Y , Baba H
  • Journal Title: Journal of Surgical Oncology Volume: 印刷中
• [Presentation] 食道扁平上皮癌におけるAKT pathwayの網羅的解析 (2013)
  • Author(s): 馬場祥史、渡邊雅之、志垣博信、小澄敬祐、原田和人、村田飛鳥、石本崇胤、岩上志朗、吉田直矢、馬場秀夫
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2013-10-24
• [Presentation] 大腸癌原発巣と遠隔転移巣におけるGenetic and Epigenetic Alterationの網羅的比較 (2013)
  • Author(s): 村田飛鳥、馬場祥史、渡邊雅之、志垣博信、岩上志朗、坂本快郎、宮本裕士、別府透、馬場秀夫
  • Organizer: 第68回日本消化器外科学会
  • Place of Presentation: サンホテルフェニックス(宮崎県)
  • Year and Date: 2013-07-17
• [Presentation] Pyrosequencing technologyを用いて食道癌におけるPIK3CA遺伝子変異の検討 (2013)
  • Author(s): 志垣博信、馬場祥史、渡邊雅之、村田飛鳥、石本崇胤、岩槻政晃、尾崎宣之、岩上志朗、坂本快郎、宮本裕士、吉田直矢、馬場秀夫
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: マリンメッセ福岡
  • Year and Date: 2013-04-12
• [Presentation] Relationship between LINE-1 methylation level, allelic imbalance and PIK3CA mutation in esophageal squamous cell carcinoma (2013)
  • Author(s): Baba Y, Watanabe M, Murata A, Shigaki H, Iwagami S, Iwatsuki M, Ishimoto T, Baba H.
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington Convention Center, Washington, DC
  • Year and Date: 2013-04-09
• [Presentation] PIK3CA mutation is associated with a favorable prognosis in esophageal squamous cell carcinoma (2013)
  • Author(s): Shigaki H, Baba Y, Watanabe M, Miyake K, Murata A, Ozaki N, Iwagami S, Ishimoto T, Iwatsuki M, Sakamoto Y, Miyamoto Y, Yoshida N, Baba H.
  • Organizer: 9th AACR-Japanese Cancer Association Joint Conference
  • Place of Presentation: Hyatt Regency Maui, Hawaii
  • Year and Date: 2013-02-22
• [Presentation] he frequency of BRAF mutation in esophageal squamous cell carcinoma detected by Pyrosequencingパイロシークエンスで検出された食道扁平上皮癌におけるBRAF変異率の検討 (2012)
  • Author(s): 志垣博信、馬場祥史、渡邊雅之、三宅慧輔、尾崎宣之、岩上志朗、石本崇胤、吉田直矢、馬場秀夫
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌(北海道)
• [Presentation] パイロシークエンスで検出された食道扁平上皮癌におけるBRAF変異率の検討. (2012)
  • Author(s): 志垣博信
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌
• [Presentation] Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma (2011)
  • Author(s): Kurashige J
  • Organizer: AACR102nd Annual Meeting 2011
  • Place of Presentation: the Orange County Convention Center in Orlando, Florida
• [Presentation] MicroRNA-29c expression as a new prognostic marker for esophageal squamous cell carcinoma (2011)
  • Author(s): Kinoshita K
  • Organizer: AACR102nd Annual Meeting 2011
  • Place of Presentation: the Orange County Convention Center in Orlando, Florida
• [Presentation] Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas: Loss of microRNA-101 promotes overexpression of histone methyltransferase EZH2 (2011)
  • Author(s): Nakahara O
  • Organizer: AACR102nd Annual Meeting 2011
  • Place of Presentation: the Orange County Convention Center in Orlando, Florida
• [Presentation] MIcroRNA-200B regulates epithelial to mesenchymal transition in gastric carcinoma (2011)
  • Author(s): Kurashige J
  • Organizer: 9th International Gastric Cancer Congress
  • Place of Presentation: Coex Center ソウル 韓国