Genomic instability in the absence of FANCJ and its possible contribution to tumorigenesis

• Project/Area Number: 21590338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: KITAO Hiroyuki 九州大学, 医学研究院, 准教授 (30368617)
• Co-Investigator(Kenkyū-buntansha): TOKUNAGA Eriko 九州大学, 大学病院, 学術研究員 (50325453) ; MORITA Masaru 九州がんセンター, 消化器外科, 医師 (30294937) ; KAKEJI Yoshihiro 九州大学, 医学研究院, 准教授 (80284488)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 分子腫瘍学 / ファンコニ貧血 / ゲノム不安定性 / FANCJ / BRCA1 / MLH1

Research Abstract

FANCJ is not only one of Fanconi anemia genes but also functions in cooperation with tumor suppressor gene products such as BRCA1 and MLH1. We found that(1) FANCJ deficient cells displayed a characteristic genomic instability phenotype. Moreover, we obtained clinical data that suggest that FANCJ affects anti-tumor effect of 5-FU in colorectal cancer patients.

Research Products

• [Journal Article] ATR-Chkl signaling pathway and homologous recombinational repair protect cells from 5-fluorouracil cytotoxicity (2012)
  • Author(s): Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto KI, Takata M, Kitao H, Maehara Y
  • Journal Title: DNA Repair Volume: 1(3) Issue: 3 Pages: 247-58
  • DOI: 10.1016/j.dnarep.2011.11.005
  • Peer Reviewed
• [Journal Article] FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer (2012)
  • Author(s): Nakanishi, et al
  • Journal Title: Annals of Surgical Oncology Volume: (In press) Issue: 11 Pages: 3627-35
  • DOI: 10.1245/s10434-012-2349-8
  • Peer Reviewed
• [Journal Article] Loss of Heterozygosity at BRCA1 Locus Is Significantly Associated with Aggressiveness and Poor Prognosis in Breast Cancer (2012)
  • Author(s): Okada, et al
  • Journal Title: Annals of Surgical Oncology Volume: (In press) Issue: 5 Pages: 1499-1507
  • DOI: 10.1245/s10434-011-2166-5
  • Peer Reviewed
• [Journal Article] FancJ/Brip1 helicase protects against genomic losses and gains invertebrate cells (2011)
  • Author(s): Kitao, et al
  • Journal Title: Genes to Cells Volume: 16 Issue: 6 Pages: 717-724
  • DOI: 10.1111/j.1365-2443.2011.01523.x
  • Peer Reviewed
• [Journal Article] Evaluation of homologous recombinational repair in chicken Blymphoma cell line, DT40 (2011)
  • Author(s): Kitao, et al
  • Journal Title: Methods in Molecular Biology Volume: 745 Pages: 293-309
• [Journal Article] Fanconi anemia : a disorder defective in the DNA damage response (2011)
  • Author(s): Kitao, Takata
  • Journal Title: International Journal of Hematology Volume: 93 Issue: 4 Pages: 417-424
  • DOI: 10.1007/s12185-011-0777-z
  • Peer Reviewed
• [Journal Article] Fanconi anemia : a disorder defective in the DNA damage response. (2011)
  • Author(s): Kitao H, Takata M
  • Journal Title: Int J Hematology Volume: (In press)
• [Journal Article] High incidence and frequency of LOH are associated with aggressive features of high-grade HER2 and triple-negative breast cancers. (2011)
  • Author(s): Tokunaga E, Okada S, Yamashita N, Akiyoshi S, Kitao H, Morita M, Kakeji Y, Maehara Y.
  • Journal Title: Breast Cancer Volume: (In press)
  • NAID: 10030981059
  • Peer Reviewed
• [Journal Article] High incidence and frequency of LOH are associated with aggressive features of high-grade HER2 and triple-negative breast cancers (2010)
  • Author(s): Tokunaga E, Okada S, Yamashita N, Akiyoshi S, Kitao H, Morita M, Kakeji Y, Maehara Y
  • Journal Title: Breast Cancer
  • NAID: 10030981059
• [Journal Article] Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes. (2010)
  • Author(s): Wu Y, Sommers JA, Suhasini AN, Leonard T, Deakyne JS, Mazin AV, Shin-Ya K, Kitao H, Brosh RM Jr.
  • Journal Title: Blood Volume: 116 Pages: 3780-91
  • Peer Reviewed
• [Journal Article] High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer (2010)
  • Author(s): Ando K, Kakeji Y, Kitao H, Iimori M, Zhao Y, Yoshida R, Oki E, Yoshinaga K, Matumoto T, Morita M, Sakaguchi Y, Maehara Y
  • Journal Title: Cancer Science Epub
  • NAID: 10026589263
  • Peer Reviewed
• [Journal Article] Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer (2010)
  • Author(s): Tokunaga E, Okada S, Kitao H, Shiotani S, Saeki H, Endo K, Morita M, Kakeji Y, Maehara Y.
  • Journal Title: Breast Cancer Epub
  • NAID: 10029407629
  • Peer Reviewed
• [Journal Article] The Fanconi anemia pathway : insights from somatic cell genetics using DT40 cell line (2009)
  • Author(s): Takata M, Iahiai M, Kitao H.
  • Journal Title: Mutation Research 668 Pages: 92-102
  • Peer Reviewed
• [Journal Article] Maehara Y. FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer
  • Author(s): Nakanishi R, Kitao H, Fujinaka Y, Yamashita N, Iimori M, Tokunaga E, Yamashita N, Morita M, Kakeji Y
  • Journal Title: Annals of Surgical Oncology(2012) in press.
• [Journal Article] Maehara Y. FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer
  • Author(s): Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto K, Takata M, Kitao H
  • Journal Title: Annals of Surgical Oncology(2012) in press
• [Journal Article] Maehara Y. ATR-Chk1 signaling pathway and homologous recombinational repair protect cells from 5-fluorouracil cytotoxicity
  • Author(s): Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto K, Takata M, Kitao H
  • Journal Title: DNA Repair(Amst) Volume: 11(3) Pages: 247-58
• [Journal Article] Evaluation of homologous recombinational repair in chicken B lymphoma cell line
  • Author(s): Kitao H, Hirano S, Takata M.
  • Journal Title: DT40. Methods Mol Biol Volume: 745
• [Journal Article] FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells
  • Author(s): Kitao H, Nanda I, Sugino RP, Kinomura A, Yamazoe M, Arakawa H, Schmid M, Innan H, Hiom K, Takata M
  • Journal Title: Genes to Cells(2011) Volume: 16(6) Pages: 714-27
• [Journal Article] Fanconi anemia : a disorder defective in the DNA damage response
  • Author(s): Kitao H, Takata M
  • Journal Title: International Journalof Hematology Volume: 4 Pages: 417-24
• [Journal Article] Copy-neutral loss of heterozygosity at the p53 locus in carcinogenesis of esophageal squamous cell carcinomas associated with p53 mutations
  • Author(s): Saeki H, Kitao H, Yoshinaga K, Nakanoko T, Kubo N, Kakeji Y, Morita M, Maehara Y.
  • Journal Title: Clinical Cancer Research Volume: 17(7) Pages: 1731-40
• [Journal Article] Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes
  • Author(s): Wu Y, Sommers JA, Suhasini AN, Leonard T, Deakyne JS, Mazin AV, Shin-Ya K, Kitao H, Brosh RM Jr
  • Journal Title: Blood Volume: 116(19) Pages: 3780-91
• [Journal Article] High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer
  • Author(s): Ando K, Kakeji Y, Kitao H, Iimori M, Zhao Y, Yoshida R, Oki E, Yoshinaga K, Matumoto T, Morita M, Sakaguchi Y, Maehara Y
  • Journal Title: Cancer Science Volume: 101(3) Pages: 639-45
  • NAID: 10026589263
• [Journal Article] Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer
  • Author(s): Tokunaga E, Okada S, Kitao H, Shiotani S, Saeki H, Endo K, Morita M, Kakeji Y, Maehara Y
  • Journal Title: Breast Cancer Volume: 18(2) Pages: 120-3
  • NAID: 10029407629
• [Journal Article] The Fanconi anemia pathway : insights from somatic cell genetics using DT40 cell line
  • Author(s): Takata M, Ishiai M, Kitao H
  • Journal Title: Mutation Research Volume: 668(1-2) Pages: 92-102
• [Presentation] Chk1-mediated S phase arrest and homologous recombinational repair protect cells from 5-FU cytotoxicity (2011)
  • Author(s): Kitao, et al
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Involvement of FancJ and Msh2 in the cellular response to 5-FU-induced DNA damages (2011)
  • Author(s): Kitao, et al
  • Organizer: 23^<rd> Annual Fanconi Anemia Research Fund Scientific Symposium
  • Place of Presentation: スペイン・バルセロナ
  • Year and Date: 2011-10-20
• [Presentation] FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells (2011)
  • Author(s): Kitao, et al
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] 5-FUにより発生するDNA損傷に対する細胞応答機構 (2011)
  • Author(s): 北尾洋之, 他
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-23
• [Presentation] 5-FUにより誘起されるDNA損傷に対する細胞応答機構 (2011)
  • Author(s): 北尾洋之、藤中良彦、飯森真人、ムンフボルド・トール、中西良太、山下奈真、松岡和明、掛地吉弘、前原喜彦
  • Organizer: 第15回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
• [Presentation] 家族性乳がん遺伝子FancJ/Brip1ヘリカーゼ欠損によって起こる大規模ゲノム欠失・増幅 (2011)
  • Author(s): 北尾洋之、高田穣、前原喜彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Homologous recombinational repair and Chk1-mediated S phase arrest protect cells from 5-FU cytotoxicity (2011)
  • Author(s): Kitao H, Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yamamoto K, Takata M, Kakeji Y, Maehara Y
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Involvement of FancJ and Msh2 in the cellular response to 5-FU-induced DNA damages (2011)
  • Author(s): Kitao H, Nakanishi R, Iimori M, Fujinaka Y, Tuul M, Yamashita N, Takata M, Kakeji Y, Maehara Y
  • Organizer: 23rd Annual Fanconi Anemia Research Fund Scientific Symposium
  • Place of Presentation: スペイン・バルセロナ
• [Presentation] Possible contribution of FancJ in the repair process of 5-FU-induced DNA damages (2010)
  • Author(s): Kitao H, Iimori M, Fujinaka Y, Nakanishi R, Tuul M, Yamashita N, Kubo N, Kakeji Y, Takata M, Maehara Y.
  • Organizer: 22^<nd> Fanconi Anemia Research Fund Annual Meeting
  • Place of Presentation: Minneapolis, MN
  • Year and Date: 2010-10-21
• [Presentation] A novel role of FancJ in the cellular response to 5-FU-induced DNA damages (2010)
  • Author(s): Kitao H, Iimori M, Fujinaka Y, Kubo N, Nakanishi R, Munkhbold T, Yoshinaga K, Tokunaga E, Saeki H, Morita M, Kakeji Y, Takata M, Maehara Y.
  • Organizer: 8^<th> AACR/JCA Conference
  • Place of Presentation: Hilton Waikoloa Village, Waikoloa, Hawaii, USA
  • Year and Date: 2010-02-09
• [Presentation] 5-FUによるファンコニ貧血経路活性化のメカニズム (2010)
  • Author(s): 北尾洋之、藤中良彦、飯森真人、ムンフボルド・トール、中西良太、山下奈真、久保信英、吉永敬士、徳永えり子、森田勝、掛地吉弘、前原喜彦
  • Organizer: 第14回日本がん分子標的治療学会
  • Place of Presentation: 東京
• [Presentation] 5-FUによるファンコニ貧血経路活性化におけるChk1の役割 (2010)
  • Author(s): 北尾洋之、飯森真人、ムンフボルド・トール、藤中良彦、久保信英、中西良太、山下奈真、吉永敬士、徳永えり子、森田勝、掛地吉弘、前原喜彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] A novel role of FancJ in the cellular response to 5-FU-induced DNA damages (2010)
  • Author(s): Kitao H, Nakanishi R, Iimori M, Fujinaka Y, Tuul M, Yamashita N, Takata M, Kakeji Y, Maehara Y
  • Organizer: 8^<th> Joint Conference of the AACR and JCA
  • Place of Presentation: ハワイ
• [Presentation] Possible contribution of FancJ in the repair process of 5-FU-induced DNA damages (2010)
  • Author(s): Kitao H, Nakanishi R, Iimori M, Fujinaka Y, Tuul M, Yamashita N, Takata M, Kakeji Y, Maehara Y
  • Organizer: 22^<nd> Annual Fanconi Anemia Research Fund Scientific Symposium
  • Place of Presentation: 米国ミネアポリス
• [Presentation] GENOME INSTABILITY PHENOTYPES INDUCED BY LOSS OF FANCJ/BRIP1 FUNCTION (2010)
  • Author(s): Kitao H, Nanda I, Kakeji Y, Maehara Y, Takata M
  • Organizer: 100^<th> Annual Meeting American Association for Cancer Research
  • Place of Presentation: 米国デンバー
• [Presentation] 5-FU感受性規定因子としてのファンコニ貧血経路とその分子機序の解明 (2009)
  • Author(s): 北尾洋之、藤中良彦、飯森真人、ムンフボルド・トール、久保信英、吉永敬士、中西良太、掛地吉弘、福島正和、高田穣、前原喜彦
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 5-FU感受性規定因子としてのファンコニ貧血経路
  • Author(s): 北尾洋之、藤中良彦、久保信英、中ノ子智徳、茂地智子、吉永敬士、ムンフボルド・トール、佐伯浩司、徳永えり子、江見泰徳、森田勝、掛地吉弘、前原喜彦
  • Organizer: 第13回日本がん分子標的治療学会
  • Place of Presentation: 徳島
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