Dysregulation of hedgehog signaling and tumorigenesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23501269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kitasato University
• Principal Investigator: MIYASHITA Toshiyuki 北里大学, 医学部, 教授 (60174182)
• Co-Investigator(Renkei-kenkyūsha): KAMEYAMA Kohzoh 北里大学, 医学部, 講師 (40214556) ; NAGAO Kazuaki 北里大学, 医学部, 助教 (60392487)
• Project Period (FY): 2011 – 2013
• Keywords: 母斑基底細胞癌症候群 / PTCH1 / 癌抑制遺伝子 / 歯原性腫瘍

Research Abstract

In order to investigate the molecular mechanism of tumor formation in NBCCS patients, we analyzed gene mutations in 10 cases of KCOT, 2 cases of meningioma and 1 case each of medulloblastoma and ovarian leiomyoma. As a result, 1 sample each of meningioma, medulloblastoma and ovarian leiomyoma had a pathogenic somatic mutation (2nd hit), whereas only one out of ten KCOT samples carried a possible pathogenic mutation.
Therefore, KCOT is suggested to arise through a mechanism distinct from that for other tumors.

Research Products

• [Journal Article] Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6 (2014)
  • Author(s): Tanaka.T., Arai, M., Jiang, X., Sugaya, S., Kanda, T., Fujii, K., Kita, K., Sugita, K., Imazeki, F., Miyashita, T., Kaneda, A., and Yokosuka, O
  • Journal Title: Int. J. Oncol Volume: 44 Pages: 1685-1690
  • DOI: 10.3892/ijo.2014.2317
  • Peer Reviewed
• [Journal Article] Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome (2013)
  • Author(s): Fujii. K., Ohashi, H. ,Suzuki, M., Hatsuse, H., Shiohama, T., Uchikawa, H., and Miyashita, T
  • Journal Title: Fam. Cancer Volume: 12 Pages: 611-614
  • Peer Reviewed
• [Journal Article] Falx cerebri calcification and microphthalmia in Gorlin syndrome (2013)
  • Author(s): Fujita Y., Fujita T., Fujii, K., and Miyashita, T
  • Journal Title: Neurol. Clin. Neurosci Volume: 1 Pages: 88-89
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of keratocystic odontogenic tumors developing in nevoid basal cell carcinoma syndrome (2013)
  • Author(s): Suzuki, M., Nagao, K., Hatsuse, H., Sasaki, R., Saito, K., Fujii, K., and Miyashita, T
  • Journal Title: Oral Surg. Oral Med. Oral Pathol. Oral Radiol Volume: 116 Pages: 348-353
  • Peer Reviewed
• [Journal Article] Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation (2012)
  • Author(s): Kijima C., Miyashita T., Suzuki M., Oka H., and Fujii K
  • Journal Title: Fam. Cancer Volume: 11 Pages: 565-570
  • Peer Reviewed
• [Journal Article] Selective haploinsufficiency of longer isoforms of PTCH1 protein can cause nevoid basal cell carcinoma syndrome (2012)
  • Author(s): Suzuki, M., Hatsuse, H., Nagao, K., Takayama, Y., Kameyama, K., Kabasawa, Y., Omura, K., Yoshida, M., Fujii, K., and Miyashita, T
  • Journal Title: J. Hum. Genet Volume: 57 Pages: 422-426
  • Peer Reviewed
• [Journal Article] Heterozygous Tandem Duplication Within the PTCH1 Gene Results in Nevoid Basal Cell Carcinoma Syndrome (2012)
  • Author(s): Kosaki, R., Nagao, K., Kameyama, K., Suzuki, M., Fujii, K., and Miyashita T
  • Journal Title: Am. J. Med. Genet A Volume: 158A Pages: 1724-1728
  • Peer Reviewed
• [Journal Article] Splicing aberration in nevoid basal cell nevus syndrome (2012)
  • Author(s): Ishitsuka, Y., Furuta, J., Miyashita, T., and Otsuka, F
  • Journal Title: Acta Derm. Venereol Volume: 92 Pages: 619-620
  • Peer Reviewed
• [Journal Article] Nationwide survey of nevoid basal cell carcinoma syndrome in Japan revealing the low frequency of basal cell carcinoma (2012)
  • Author(s): Endo, M., Fujii, K., Sugita, K., Saito, K., Kohno, Y., and Miyashita, T
  • Journal Title: Am. J. Med. Genet A Volume: 158A Pages: 351-357
  • Peer Reviewed
• [Journal Article] Entire PTCH1 deletion is a common event in point mutation-negative cases with nevoid basal cell carcinoma syndrome in Japan (2011)
  • Author(s): Nagao, K., Fujii, K., Saito, K., Sugita, K., Endo, M., Motojima, T., Hatsuse, H. and Miyashita, T
  • Journal Title: Clin. Genet Volume: 79 Pages: 196-198
  • Peer Reviewed
• [Presentation] Functional analysis of a sonic hedgehog signaling pathway inhibitor SUFU (2013)
  • Author(s): 長尾和右、宮下俊之
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] 母斑基底細胞癌症候群で見出されたスプライシング変異と異常mRNA の分解 (2012)
  • Author(s): 志村将人、鈴木麻衣子、初瀬洋美、長尾和右、高山吉永、亀山孝三、藤井克則、宮下俊之
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] PTCH2とSUFU 遺伝子に配偶子変異をもつ母斑基底細胞癌症候群の検討 (2012)
  • Author(s): 鈴木麻衣子、長尾和右、高山吉永、岡秀宏、藤井克則、宮下俊之
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Suppressor of fused (SUFU)遺伝子の配偶子変異は高い髄芽腫の発症リスクをもたらす (2012)
  • Author(s): 鈴木麻衣子、宮下俊之、木島千尋、岡秀宏、藤井清孝
  • Organizer: 第16回日本家族性腫瘍学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20120615-16
• [Presentation] 母斑基底細胞癌症候群の分子遺伝学 (2011)
  • Author(s): 宮下俊之
  • Organizer: 第56回日本人類遺伝学会・第11回東アジア人類遺伝学会共同大会
  • Place of Presentation: 千葉
  • Year and Date: 20111109-12
• [Presentation] 日本における母斑性基底細胞癌症候群における基底細胞癌発症率 (2011)
  • Author(s): 藤井克則、宮下俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-05
• [Presentation] 母斑基底細胞癌症候群に発症した歯原性腫瘍の遺伝子解析 (2011)
  • Author(s): 宮下俊之、桐生麻衣子、佐々木亮、齋藤加代子、藤井克則
  • Organizer: 遺伝医学合同学術集会
  • Place of Presentation: 京都
  • Year and Date: 20110616-19
• [Remarks] ホームページ等
  • URL: http://www.med.kitasato-u.ac.jp/~molgen/