Effects of genomic damage by chemo-radiation therapy during childhood for secondary malignancy and genetic inheritance

• Project/Area Number: 15K15644
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Hiroshima University
• Principal Investigator: HIYAMA EISO 広島大学, 自然科学研究支援開発センター, 教授 (00218744)
• Co-Investigator(Kenkyū-buntansha): KURIHARA SHO 広島大学, 大学病院, 医科診療医 (40724894)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: ゲノム / 放射線 / がん / 遺伝学 / 遺伝子

Outline of Final Research Achievements

Genomic sequencing analysis was performed in the 15 groups consisting of the survivor who had undergone the treatment for childhood cancer after 1980, its partner, and descendant. Among 6 survivors whose tumors had been advanced of stage, exome analysis revealed 2, 9, 12, 16, 32, and 84 mutations occurred after treatment, respectively. Among 4 survivors including 2 survivors with secondary malignancy, whole genome sequencing revealed 126、87、73, 198 mutations occurred after treatment. The genomic analysis of 3 descendants using exome analysis, 3 of 84, 1 of 12, and 0 of 34 mutations were suspected to be inherited, respectively. The exome analysis of 4 cases with secondary malignancies showed no common mutations nor mutation signatures.

Research Products

• [Journal Article] Clinical prognostic value of DNA methylation in hepatoblastoma: Four novel tumor suppressor candidates (2016)
  • Author(s): Honda S, Minato M, Suzuki H, Fujiyoshi M, Miyagi H, Haruta M, Kaneko Y, Hatanaka KC, Hiyama E, Kamijo T, Okada T, Taketomi A
  • Journal Title: Cancer Science Volume: in press Issue: 6 Pages: 812-819
  • DOI: 10.1111/cas.12928
  • NAID: 120005828475
  • Peer Reviewed / Open Access
• [Journal Article] Circulating free DNA as non-invasive diagnostic biomarker for childhood solid tumors (2015)
  • Author(s): Kurihara S, Ueda Y, Onitake Y, Sueda T, Ohta E, Morihara N, Hirano S, Irisuna F, Hiyama E
  • Journal Title: Journal of Pediatric Surgery Volume: 50 Issue: 12 Pages: 2094-2097
  • DOI: 10.1016/j.jpedsurg.2015.08.033
  • Peer Reviewed / Open Access
• [Journal Article] Mortality and morbidity in primarily resected hepatoblastomas in Japan: Experience of the JPLT (Japanese Study Group for Pediatric Liver Tumor) trials (2015)
  • Author(s): Hiyama E, Hishiki T, Watanabe K, Ida K, Yano M, Oue T, Iehara T, Hoshino K, Koh K, Tanaka Y, Kurihara S, Ueda Y, Onitake Y
  • Journal Title: Journal of Pediatric Surgery Volume: 50 Issue: 12 Pages: 2098-2101
  • DOI: 10.1016/j.jpedsurg.2015.08.035
  • Peer Reviewed / Open Access
• [Journal Article] Direct Lipido-Metabolomics of Single Floating Cells for Analysis of Circulating Tumor Cells by Live Single-cell Mass Spectrometry (2015)
  • Author(s): Hiyama E, Ali A, Amer S, Harada T, Shimamoto K, Furushima R, Abouleila Y, Emara S, Masujima T
  • Journal Title: Analytical Sciences Volume: 31 Issue: 12 Pages: 1215-1217
  • DOI: 10.2116/analsci.31.1215
  • NAID: 130005129718
  • ISSN: 0910-6340, 1348-2246
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model (2015)
  • Author(s): Czauderna P, Haeberle B, Hiyama E, Rangaswami A, Krailo M, Maibach R, Rinaldi E, Feng Y, Aronson D, Malogolowkin M, Yoshimura K, Leuschner I, Lopez-Terrada D, Hishiki T, Perilongo G, von Schweinitz D, Schmid I, Watanabe K, Derosa M, Meyers R
  • Journal Title: European Journal of Cancer Volume: 1 Pages: 92-101
  • DOI: 10.1016/j.ejca.2015.09.023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Exome sequencing of hepatoblastoma identifies biological signatures and protential therapeutic targets (2016)
  • Author(s): Hiyama E
  • Organizer: International Pediatric Liver Tumor Symposium
  • Place of Presentation: Texas, USA
  • Year and Date: 2016-02-25
  • Int'l Joint Research
• [Presentation] 小児肝がんに対するゲノム解析と国際共同臨床試験へのアプローチ (2015)
  • Author(s): 檜山 英三
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2015-10-29
• [Presentation] Prediction of prognosis by preoperative chemotherapy response in hepatoblastoma patients treated by JPLT-2 protocol (2015)
  • Author(s): Hiyama E, Hishiki T, Ida K, Watanabe K, Oue T, Yano M, Hoshino K, Iehara T, Koh K, Tanaka Y, Kurihara S, Ueda Y
  • Organizer: SIOP 2015
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Integrated exome analysis in childhood hepatoblastoma: Biological approach for molecular targeting (2015)
  • Author(s): Hiyama E, Kurihara S, Onitake Y, Ueda Y, Morihara N, Fukuba I, Komatsu R
  • Organizer: SIOP 2015
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Changes in the clinical features of neuroblastoma 10 years after the cessation of mass screening in Japan (2015)
  • Author(s): Yoneda A, tajiri T, Hiyama E, Iehara T, Hishiki T, Sugito K, Hayashi Y, Maeda K, Yonekura T
  • Organizer: SIOP 2015
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Congenital hepatoblastoma in JPLT-2 study (2015)
  • Author(s): Watanabe K, Hishiki T, Ida K, Oue T, Yano M, Hoshino K, Iehara T, Koh K, Tanaka Y, Hiyama E
  • Organizer: SIOP 2015
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Survival and late effects in the risk-stratified hepatoblastoma patients treated by JPLT-2 protocol (2015)
  • Author(s): Hiyama E, Kurihara S, Ueda Y, Hishiki T, Ida K, Iehara T, Oue T, Yano M, Watanabe K, Hoshino K, Ko K, Tanaka Y
  • Organizer: 2015 ASCO Annual Meeting
  • Place of Presentation: Chicago, U.S.A
  • Year and Date: 2015-05-29
  • Int'l Joint Research
• [Presentation] Circulating free DNA as non-invasive diagnostic biomarker for childhood solid tumors (2015)
  • Author(s): Kurihara S, Ueda Y, Onitake Y, Sueda T, Ohta E, Morihara N, Hirano S, Irisuna F, Hiyama E
  • Organizer: 48th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Jeju, South Kore
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Mortality and morbidity in primarily resected hepatoblastomas in Japan: experience of JPLT (Japanese study group for pediatric liver tumor) trials (2015)
  • Author(s): Hiyama E, Hishiki T, Watanabe K, Ida K, Yano M, Oue T, Iehara T, Hoshino K, Koh K, Tanaka Y, Kurihara S, Ueda Y, Onitake Y
  • Organizer: 48th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Jeju, South Kore
  • Year and Date: 2015-05-17
  • Int'l Joint Research