Analysis of tumor clonality using SNPs surrounding BRAF gene and its association with clinicopathological features

• Project/Area Number: 19790651
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Endocrinology
• Research Institution: Nagasaki University
• Principal Investigator: ROGOUNOVITCH Tatiana Nagasaki University, 大学院・医歯薬学総合研究科, 助教 (30423643)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,570,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: 甲状腺乳頭癌 / BRAF変異 / クローナリティ / アレル / 対立遺伝子 / BRAF / 甲状腺癌 / 遺伝子多型

Research Abstract

甲状腺乳頭癌(PTC)のクローナリティを、X染色体上のHUMARA遺伝子の不活性化を指標として解析したところ、多くのPTCは単クローン性であったが、多クローン性のPTCも存在した。次に、BRAF変異とその周囲の遺伝子多型部位を指標として用いたところ、驚くべき事に、単クローン性、多クローン性の両方の腫瘍に、片アレルのみ、もしくは両アレルに変異BRAFが見つかった(ただし、ホモ接合性ではない)。BRAF変異はおそらくヘテロ接合性、片アレルに生じるが、腫瘍の進展に伴い、相同染色体組換えの様なメカニズムにより、別のアレルに移る可能性が示唆された。また、単一の腫瘍といえども、複数の細胞に遺伝子変異が生じた多クローン性の起源を持つものもあると考えられた。

Research Products

• [Journal Article] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma (2009)
  • Author(s): Akulevitch N, Saenko V, Rogounovitch T, Drozd V, Lushnikov E, Ivanov V, Mitsutake N, Kominami R, Yamashita S
  • Journal Title: Endocr Relat Cancer (in press)
  • Peer Reviewed
• [Journal Article] Mutation analysis of RAP1 gene in papillary thyroid carcinomas (2009)
  • Author(s): Matsuse M, Mitsutake N, Rogounovitch T, Saenko V, Nakazawa Y, Lushnikov E, Yamashita S
  • Journal Title: Endocrine Journal 56 Pages: 161-164
  • NAID: 10025610615
  • Peer Reviewed
• [Journal Article] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma (2009)
  • Author(s): Akulevich N, et.al.
  • Journal Title: Endocr Relat Cancer (印刷中)
  • Peer Reviewed
• [Journal Article] Mutation analysis of RAP1 gene in papillary thyroid carcinomas (2009)
  • Author(s): Matsuse M, et.al.
  • Journal Title: Endocr J. 56 Pages: 161-164
  • Peer Reviewed
• [Journal Article] Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from radiation-induced damage (2008)
  • Author(s): Nakazawa Y, Saenko V, Rogounovitch T, Suzuki K, Mitsutake N, Matsuse M, Yamashita S
  • Journal Title: Int J Radiat Oncol Biol Phys 71 Pages: 567-577
  • Peer Reviewed
• [Journal Article] Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells (2008)
  • Author(s): Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI, Nakazawa Y, Hayashi T, Ohtsuru A, Yamashita S
  • Journal Title: Cancer Sci 99 Pages: 1147-1154
  • Peer Reviewed
• [Journal Article] A novel role for thyroid hormone receptor beta in cellular radiosensitivity (2008)
  • Author(s): Matsuse M, Saenko V, Sedliarou I, Rogounovitch T, Nakazawa Y, Mitsutake N, Akulevich N, Namba H, Yamashita S
  • Journal Title: J Radiat Res(Tokyo) 49 Pages: 17-27
  • NAID: 110006570524
  • Peer Reviewed
• [Journal Article] Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from radiation-induced damage (2008)
  • Author(s): Nakazawa Y, et.al.
  • Journal Title: Int J Radiat Oncol Biol Phys 71 Pages: 567-577
  • Peer Reviewed
• [Journal Article] Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells (2008)
  • Author(s): Takakura S, et.al.
  • Journal Title: Cancer Sci 99 Pages: 1147-1154
  • Peer Reviewed
• [Journal Article] Overexpression of wild-type THRbeta1 suppresses the growth and invasiveness of human papillary thyroid cancer cells (2007)
  • Author(s): Sedliarou I, Matsuse M, Saenko V, Rogounovitch T, Nakazawa Y, Mitsutake N, Namba H, Nagayama Y, Yamashita S
  • Journal Title: Anticancer Res 27 Pages: 3999-4009
  • Peer Reviewed
• [Journal Article] The cytoplasmic expression of MUC1 in papillary thyroid carcinoma of different histological variants and its correlation with cyclin D1 overexpression (2007)
  • Author(s): Abrosimov A, Saenko V, Meirmanov S, Nakashima M, Rogounovitch T, Shkurko O, Lushnikov E, Mitsutake N, Namba H, Yamashita S
  • Journal Title: Endocr Pathol 18 Pages: 68-75
  • Peer Reviewed
• [Journal Article] Different structural components of conventional papillary thyroid carcinoma display mostly identical BRAF status (2007)
  • Author(s): Abrosimov A, Saenko V, Rogounovitch T, Namba H, Lushnikov E, Mitsutake N, Yamashita S
  • Journal Title: Int J Cancer 102 Pages: 196-200
  • Peer Reviewed
• [Journal Article] Overexpression of wild-type THRbetal suppresses the growth and invasiveness of human papillary thyroid cancer cells. (2007)
  • Author(s): Sedliarou I, et. al.
  • Journal Title: Anticancer Res. 27 Pages: 3999-4009
  • Peer Reviewed
• [Journal Article] A novel role for thyroid hormone receptor beta in cellular radiosensitivity. (2007)
  • Author(s): Matsuse M, et. al.
  • Journal Title: J Radiat Res 49 Pages: 17-27
  • Peer Reviewed
• [Journal Article] The cytoplasmatic expression of MUC1 in papillary thyroid carcinoma of different histological variants and its correlation with cyclin D1 overexpression. (2007)
  • Author(s): Abrosimov A, et. al.
  • Journal Title: Endocr Pathol 18 Pages: 68-75
  • Peer Reviewed
• [Journal Article] Different structural components of conventional papillary thyroid carcinoma display mostly identical BRAF status (2007)
  • Author(s): Abrosimov A, et. al.
  • Journal Title: Int J Cancer 120 Pages: 196-200
  • Peer Reviewed
• [Presentation] Molecular and clinico-pathological analysis of pediatric thyroid cancers in Belarus (2008)
  • Author(s): Tatiana Rogounovitch
  • Organizer: ENDO 2008, the 90th Annual Meeting of the Endocrine Society
  • Place of Presentation: San Francisco, USA
• [Presentation] Thyroid cancer susceptibility : implication of ATM and TP53 genetic variations in papillary thyroid carcinoma of different etiology (2008)
  • Author(s): Natallia Akulevich
  • Organizer: ENDO 2008, the 90th Annual Meeting of the Endocrine Society
  • Place of Presentation: San Francisco, USA
• [Presentation] Molecular and clinico-pathological features of sporadic pediatric thyroid cancers from Belarus (2008)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Variations in the ATM and TP53 as a potential genetic markers of papillary thyroid carcinoma of different etiology (2008)
  • Author(s): Natallia Akulevich
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Preoperative evaluation of thyroid nodules by molecular analysis of FNAB materials (2008)
  • Author(s): ウラジミールサエンコ
  • Organizer: 第51回日本甲状腺学会
  • Place of Presentation: 宇都宮
• [Presentation] 甲状腺乳頭癌におけるRAP1遺伝子変異 (2008)
  • Author(s): 松瀬美智子
  • Organizer: 第51回日本甲状腺学会
  • Place of Presentation: 宇都宮
• [Presentation] 甲状腺細胞および間質細胞間の相互作用による放射線誘発DNA損傷の低減 (2008)
  • Author(s): 中沢由華
  • Organizer: 第51回日本甲状腺学会
  • Place of Presentation: 宇都宮
• [Presentation] Molecular and clinico-pathological analysis of pediatric thyroid cancers in Belarus (2008)
  • Author(s): Tatiana Rogounovitch
  • Organizer: ENDO 2008, the 90^<th> Annual Meeting of the Endocrine Society
  • Place of Presentation: San Francisco, USA
• [Presentation] Thyroid cancer susceptibility : implication of ATM and TP53 genetic variations in papillary thyroid carcinoma of different etiology (2008)
  • Author(s): Natallia Akulevich
  • Organizer: ENDO 2008, the 90^<th> Annual Meeting of the Endocrine Society
  • Place of Presentation: San Francisco, USA
• [Presentation] Molecular and clinico-pathological features of sporadic pediatric thyroid cancers from Belarus (2008)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 弟81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Variations in the ATM and TP53 as a potential genetic markers of papillary thyroid carcinoma of different etiology (2008)
  • Author(s): Natallia Akulevich
  • Organizer: 弟81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Preoperative evaluation of thyroid nodules by molecular analysis of FNAB materials (2008)
  • Author(s): ウラジミールサエンコ
  • Organizer: 弟51回日本甲状腺学会
  • Place of Presentation: 宇都宮
• [Presentation] 甲状腺乳頭癌におけるRAP1遺伝子変異 (2008)
  • Author(s): 松瀬美智子
  • Organizer: 弟51回日本甲状腺学会
  • Place of Presentation: 宇都宮
• [Presentation] 甲状腺細胞および間質細胞間の相互作用による放射線誘発DNA損傷の低減 (2008)
  • Author(s): 中沢由華
  • Organizer: 弟51回日本甲状腺学会
  • Place of Presentation: 宇都宮
• [Presentation] Association of SNPs in the ATM and MTF-1 genes with the risk of human papillary thyroid carcinomas (2007)
  • Author(s): Natallia Akulevich
  • Organizer: American Thyroid Association 78th Annual Meeting
  • Place of Presentation: New York, USA
• [Presentation] Peculiarities of distribution of genetic patterns of mutant BRAF in papillary thyroid carcinoma tissues (2007)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] A case of thyroid hormone resistance with novel type of abnormal THRB1 transcripts (2007)
  • Author(s): Natallia Akulevich
  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] Overexpression of wild-type THRB1 suppresses the growth and invasiveness of human papillary thyroid cancer cells (2007)
  • Author(s): Ilya Sedliarou
  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] Clonality of papillary thyroid carcinomas harboring BRAF mutation (2007)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 第50回日本甲状腺学
  • Place of Presentation: 神戸
• [Presentation] Efficacy of molecular tests in preoperative diagnosis of thyroid nodules (2007)
  • Author(s): Vladimir Saenko
  • Organizer: 第50回日本甲状腺学
  • Place of Presentation: 神戸
• [Presentation] Association of SNPs in the ATM and MTF-1 genes with the risk of human papillary thyroid carcinomas (2007)
  • Author(s): Natallia Akulevich
  • Organizer: American Thyroid Association 78th Annual Meeting
  • Place of Presentation: USA
• [Presentation] Peculiarities of distribution of genetic patterns of mutant BRAF in papillary thyroid carcinoma tissues (2007)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 弟80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] A case of thyroid hormone resistance with novel type of abnormal THRB1 transcripts (2007)
  • Author(s): Natallia Akulevich
  • Organizer: 弟80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] Overexpression of wild-type THRB1 suppresses the growth and invasiveness of human papillary thyroid cancer cells (2007)
  • Author(s): Ilya Sedliarou
  • Organizer: 弟80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Presentation] Clonality of papillary thyroid carcinomas harboring BRAF mutation (2007)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 弟50回日本甲状腺学会
  • Place of Presentation: 神戸
• [Presentation] Efficacy of molecular tests in preoperative diagnosis of thyroid nodules (2007)
  • Author(s): Vladimir Saenko
  • Organizer: 弟50回日本甲状腺学会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/adi-pphy/
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/adi-pphy/