体系的遺伝子異常解析に基づく乳癌・甲状腺癌の遺伝子診断法の開発

• Project/Area Number: 12217141
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nippon Medical School
• Principal Investigator: 江見 充 日本医科大学, 老人病研究所, 教授 (90221118)
• Co-Investigator(Kenkyū-buntansha): 霞 冨士雄 (霞 富士雄) 癌研究会附属病院(外科), 部長 (40085593)
• Project Period (FY): 2000 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥61,200,000 (Direct Cost: ¥61,200,000); Fiscal Year 2004: ¥12,200,000 (Direct Cost: ¥12,200,000); Fiscal Year 2003: ¥12,200,000 (Direct Cost: ¥12,200,000); Fiscal Year 2002: ¥12,000,000 (Direct Cost: ¥12,000,000); Fiscal Year 2001: ¥12,800,000 (Direct Cost: ¥12,800,000); Fiscal Year 2000: ¥12,000,000 (Direct Cost: ¥12,000,000)
• Keywords: 遺伝子発現 / 乳癌 / 甲状腺癌 / 遺伝子診断 / 予後因子 / マイクロアレイ / 技術移転 / がん関連遺伝子 / 染色体欠失

Research Abstract

1.「乳癌・甲状腺癌の遺伝子診断の開発と技術移転」:乳癌術後5年間の追跡調査と遺伝子解析により、n0乳癌群、n1・2乳癌群、高容量化学療法乳癌群のについて術後予知因子となる染色体欠失(LOH)を同定したが、これに基づき、毎週約10症例(約2年間で約1000症例)の遺伝子診断を継続し、遺伝子診断による症例の層別化と高危険群の予測を実施し、基礎研究から臨床実施への技術移転を行なった。
2.「体系的遺伝子発現解析」
乳癌・甲状腺癌の新鮮凍結保存検体から高純度RNAを抽出し、RNA増幅を行い、高密度cDNAマイクロアレイを用いて、約2万5千種の遺伝子の癌組織での発現プロファイル解析を行い、乳癌および甲状腺乳頭癌において術後予後と関連して発現異常を呈する遺伝子群を同定した。
(1)乳癌;a)ER陰性乳癌、b)n0乳癌、c)T2乳癌、d)ER陽性乳癌の4群について予後良好群と予後不良群に分類し、予後に関与する遺伝子の発現異常を検討し、ER陰性乳癌、n0乳癌、T2乳癌、ER陽性乳癌でそれぞれ18種、10種、10種、10種の予後予測遺伝子を選択した。これらの遺伝子セットを用いて予後予測システムを構築した。テスト症例の予後は、これらのシステムにとよる予後予測と高い精度で一致した。
(2)甲状腺癌:a)甲状腺乳頭癌15例、およびb)甲状腺未分化癌11例についてcDNAマイクロアレイ解析とreal-time RT-PCRおよび免疫組織学的染色を行ない、乳頭癌では、TIMP-1(Tissue Inhibitor of Metalloproteinase 1)、転写因子E2F1等の遺伝子群の、また、甲状腺未分化癌では、GDI2、StathminおよびDestrin等の遺伝子群の癌部での強発現を同定した。後者群は甲状腺癌の未分化転化への関与機序を細胞機能レベルで検討している。

Research Products

• [Journal Article] Over expressed in Anaplastic Thyroid Cancer-1(OEATC-1), as a novel responsible gene for anaplastic thyroid cancer. (2005)
  • Author(s): Onda, M., Mizutani, K., Asaka, S., Akaishi, J., Miyamoto, S., Yoshida, A., Nagahama, M., Ito., K., Emi M.
  • Journal Title: Cancer (印刷中)
• [Journal Article] Identification of RAI13 as a therapeutic target for breast cancer. (2005)
  • Author(s): Nagahata, T., Sato, T., Tomura, A., Onda, M., Nishijkawa, K., Emi, M.
  • Journal Title: Endocrine-Related Cancer 12 Pages: 65-79
• [Journal Article] Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25344 genes. (2004)
  • Author(s): Onda, M., Emi, M., Yoshida, A., Mikyamoto, S., Akaishi, J., Asaka, S., Mizutani, K., Shimizu, K., Nagahama, M., Ito, K., Tanaka, T., Tsunoda, T.
  • Journal Title: Endocrine-Related Cancer 11 Pages: 843-854
• [Journal Article] Expression profiling to predict postoperative prognosis for estrogen receptor-negative breast cancers by analysis of 25,344 genes on a cDNA microarray (2004)
  • Author(s): Nagahata, T., Onda, M., Emi, M., Nagai, H., Tsumagari, K., Fujimoto, T., Hirano, A., Sato, T., Nishikawa, K., Akiyama, F., Sakamoto, G., Kasumi, F., Miki, Y., Tanaka.T., Tsunoda T.
  • Journal Title: Cancer Sci. 95 Pages: 210-225
• [Journal Article] Gene expression patterns as marker for 5-year postoperative prognosis of primary breast cancers (2004)
  • Author(s): Onda, M., Emi, M., Nagai, H., Nagahata, T., Tsumagari, K., Fujimoto, T., Akiyama, F., Sakamoto, G., Makita, M., Kasumi, F., Miki, Y., Tanaka, T., Tsunoda, T., Nakamuara.Y.
  • Journal Title: J.Cancer Res.Clin.Oncol. 130 Pages: 537-545
• [Journal Article] Up-regulation of Transcriptional Factor E2F1 in Papillary and Anaplastic Thyroid Cancers (2004)
  • Author(s): Onda, M., Nagai, H., Yoshida, A., Miyamoto, S., Akaishi, J., Asaka, S., Takatsu, K., Shimizu, K., Nagahama, M., Ito, K., Emi, M.
  • Journal Title: J.Hum.Genet. 49 Pages: 312-318
• [Journal Article] Amplification, Up-regulation and Over-expression of Dvl-1, the Human Counterpart of the Drosophila disheveled gene, in Primary Breast Cancers. (2003)
  • Author(s): Nagahata, T., Shimada, T., Harada, A., Nagai, H., Onda, M., Yokoyama, S., Shiba, T., Jin, E., Kawanami, O., Emi, M.
  • Journal Title: Cancer Sci. 94 Pages: 515-518
• [Journal Article] Upregulation and Overexpression of Human X-box binding protein 1(hXBP-1) Gene in Primary Breast Cancers. (2003)
  • Author(s): Fujimoto, T., Onda, M., Nagai, H., Nagahata, T., Ogawa, K., Emi, M.
  • Journal Title: Breast Cancer 102 Pages: 301-306
• [Journal Article] Correlation of Allelic Losses and Clinicopathological Factors in 504 Primary Breast Cancers (2002)
  • Author(s): Nagahata, T., Emi, M., Hirano, A., Utada, Y., Tsuchiya, S., Takahashi, K., Tada, T., Makita, M., Kasumi, F., Akiyama, F., Sakamoto, G., Nakamura, Y.
  • Journal Title: Breast Cancer 9 Pages: 208-215
• [Journal Article] Molecular Diagnosis for Breast Cancer (2002)
  • Author(s): Nagahata, T., Kosaka, N., Shimizu, M., Emi, M.
  • Journal Title: Jpn.Med.Assoc.J. 45 Pages: 265-270
• [Journal Article] Association of Allelic loss at 8p22 with Poor prognosis among Breast Cancers Cases treated with high-dose adjuvant chemotherapy (2002)
  • Author(s): Tsuneizumi, M., Emi, M., Hirano, A., Utada, Y., Tsumagari, K., Takahashi, K., Kasumi, F., Akiyama, F., Sakamoto, G., Kazui, T., Nakamura, Y.
  • Journal Title: Cancer Lett 180 Pages: 75-82
• [Journal Article] Differential Expression of Multiple Isoforms of the ELKS mRNAs Involved in a Papillary Thyroid Carcinoma. (2002)
  • Author(s): Nakata, T., Yokota, T., Emi, M., Minami, S.
  • Journal Title: Genes, Chrome.Cancer 35 Pages: 30-37
• [Journal Article] 癌の遺伝要因の解明と現状 (2002)
  • Author(s): 永井尚生, 江見 充
  • Journal Title: 医学のあゆみ Pages: 869-876
• [Journal Article] Allelotyping of Follicular Thyroid Carcinoma : Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q (2001)
  • Author(s): Kitamura, Y., Shimizu, K., Ito, K., Tanaka, S., Emi, M.
  • Journal Title: J.Clin.Endocrinol.Metab. 66 Pages: 4268-4272
• [Journal Article] Allelic Loses of loci at 3p25.1, 8p22, 13q12, 17p13.3 and 22g13 Correlate with Postoperative Recurrence in Breast Cancer (2001)
  • Author(s): Hirano, A., Emi, M., Tsuneizumi, M., Utada, Y., Yoshimoto, M., Kasumi, F., Akiyama, F., Sakamoto, G., Haga, S., Kajiwara, T., Nakamura, Y.
  • Journal Title: Clin.Cancer Res 7 Pages: 876-882
• [Journal Article] Allelic Losses as Prognostic Markers for Breast Cancers (2001)
  • Author(s): Hirano, A., Utada, Y., Haga, S., Kajiwara, T., Sakamoto, G., Kasumi, F., Nakamura, Y., Emi, M.
  • Journal Title: Int.J.Clin.Oncol. 6 Pages: 6-12
• [Journal Article] 乳癌の遺伝子診断-癌 遺伝子診断の臨床への応用 (2001)
  • Author(s): 長幡武光, 江見 充
  • Journal Title: 癌の臨床 Pages: 501-508
• [Journal Article] 乳癌の遺伝子診断(特集-「乳癌診断・治療の現状と展望」) (2001)
  • Author(s): 長幡武光, 江見 充
  • Journal Title: 日本医師会雑誌 Pages: 1731-1734
• [Journal Article] Allelic Loss at the 8p22 Region as a Prognostic Factor in Large and Estrogen Receptor-Negative Breast Carcinomas (2000)
  • Author(s): Utada, Y., Haga, S., Kajiwara, T., Kasumi, F., Sakamoto, G., Nakamura, Emi, M.
  • Journal Title: Genes, Chrom.Cancer 27 Pages: 244-251
• [Journal Article] Allelotyping of Anaplastic Thyroid Carcinoma : Frequent Allelic Losses on 1q, 9p, 11, 17, 19p, and 22q. (2000)
  • Author(s): Kitamura, Y., Shimizu, K., Tanaka, S., Ito, K., Emi, M.
  • Journal Title: Genes, Chrom.Cancer 27 Pages: 244-251
• [Journal Article] Association of Allelic Loss on 1q, 4p, 7q, 9p, 9q, and 16q with Postoperative Death in Papillary Thyroid Carcinoma (2000)
  • Author(s): Kitamura, Y., Shimizu, K., Tanaka, S., Ito, K., Emi, M.
  • Journal Title: Clin.Cancer Res 6 Pages: 1819-1825
• [Journal Article] 染色体欠失の遺伝子診断(特集-乳癌の診断と治療) (2000)
  • Author(s): 歌田貴仁, 江見 充
  • Journal Title: 日本臨牀 Pages: 473-477
• [Book] 医学のあゆみ 別冊state of arts「乳癌のLOHと遺伝子診断」 (2004)
  • Author(s): 音田正光, 江見 充
  • Total Pages: 11-14
• [Book] 乳癌診療TIPS&TRAPS「乳癌における遺伝子研究の現況と展望」 (2004)
  • Author(s): 浅香晋一, 音田正光, 長播武光, 江見 充
  • Total Pages: 6-7
• [Book] 乳癌診断、治療のコツと落とし穴「cDNAマイクロアレイを用いた乳癌術後診断」 (2004)
  • Author(s): 浅香晋一, 江見 充, 音田正光, 長幡武光, 三木義男, 坂元吾偉, 霞富士雄
  • Publisher: (印刷中)
• [Book] 乳癌の最新医療 先端医療技術研究「多型性DNAマーカーによる乳癌の予後診断」 (2003)
  • Author(s): 音田正光, 長幡武光, 江見 充
  • Total Pages: 69-71
• [Patent(Industrial Property Rights)] RAI3遺伝子発現抑制物質 (2004)
  • Inventor(s): 長幡 武光, 江見 充
  • Industrial Property Rights Holder: 日本化薬株式会社, 日本医科大学
  • Industrial Property Number: 特願2004-110232
  • Filing Date: 2004-04-02
• [Patent(Industrial Property Rights)] 乳癌の術後予後予測に関与する遺伝子 (2004)
  • Inventor(s): 江見 充, 音田 正光, 永井 尚生
  • Industrial Property Rights Holder: 日本医科大学, (株)三菱化学ビーシーエル, (株)三菱レイヨン
  • Industrial Property Number: 特願2004-318585
  • Filing Date: 2004-11-01
• [Patent(Industrial Property Rights)] 腫瘍抑制遺伝子 (2001)
  • Inventor(s): 原田 晴仁, 永井 尚生, 常泉 道子, 三上 巌, 江面 陽一, 江見 充, 菅野 純夫
  • Industrial Property Rights Holder: 江見 充, (株)先端生命科学研究所
  • Industrial Property Number: 特願2001-264929
  • Filing Date: 2001-07-31
  • Acquisition Date: 2003-02-18
• [Publications] Konishi, N.: "Genetic Mapping of allelic loss on chromosome 6q within heterogeneous prostate carcinoma."Cancer Science. 94(9). 764-768 (2003)
• [Publications] Yokota, T.: "A family with spinal anaplastic ependymoma : evidence of loss of chromosome 22q in tumor."J.Hum.Genet.. 48(11). 598-602 (2003)
• [Publications] Nakagawachi, T.: "Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA metyltransferase (MGMT) gene expression in human cancer."Oncogene. 22(55). 8835-8844 (2003)
• [Publications] Nagai, H.: "DNA Alterations during Multi-step Development of Human Hepatocellular Carcinomas Revealed by Laser Capture Microdissection."Hepatology Res.. 26(3). 199-208 (2003)
• [Publications] Nagai, H.: "Down-regulation in Human Cancers of DRHC, a Novel Helicase-like Gene from 17q25.1 That Inhibit Cell Growth."Cancer Lett.. 193(1). 41-47 (2003)
• [Publications] Nagai, H.: "Hypermethylation Associated with Inactivation of the SOCS-1 Gene, a JAK/STAT Inhibitor, in Human Hepatoblastomas."J.Hum.Genet.. 48(2). 65-69 (2003)
• [Publications] Fujimoto, T.: "Upregulation and Overexpression of Human X-box binding protein 1(hXBP-1) Gene in Primary Breast Cancers."Breast Cancer. 10(4). 301-306 (2003)
• [Publications] Hatta, M.: "Down-regulation of members of glycolpid-enriched membrane raft gene family, MAL and BENE, in cervical squamous cell cancers."J.Obstetr.Gynecol.Res.. 30(1). 53-58 (2003)
• [Publications] Nagahata, T.: "Amplification, Up-regulation and Over-expression of Dvl-1, the Human Counterpart of the Drosophila disheveled gene, in Primary Breast Cancers."Cancer Science. 94(6). 515-518 (2003)
• [Publications] Okino, K.: "Up-regulation and overproduction of DVL-1, the Human Counterpart of the Drosophila disheveled gene, in cervical squamous cell carcinoma."Oncol.Rep.. 10(5). 1219-1223 (2003)
• [Publications] Nagahata, T.: "Expression profiling to predict postoperative prognosis for estrogen receptor-negative breast cancers by analysis of 25,344 genes on a cDNA microarray."Cancer Science. (In press). (2004)
• [Publications] Komazaki, T.: "Hypermethylation Associated with Inactivation of the SOCS-1 Gene, a JAK/STAT Inhibitor, in Human Pancreatic Cancer."Jpn.J.Clinical Oncol.. (In press). (2004)
• [Publications] Hirata, T.: "Amplification, Up-regulation and Over-expression of C3G (CRK SH3 Domain-Binding Guanine Nucleotide-Releasing Factor) in Lung Cancer."J.Hum.Genet.. 49(In press). (2004)
• [Publications] Nagai, H.: "Characterization of Liver-Cirrhosis Nodules by Analysis of Gene-expression profiles and Patterns of Allelic Loss."J.Hum.Genet.. 49(In press). (2004)
• [Publications] Onda, M.: "Up-regulation of Transcriptional Factor E2F1 in Papillary and Anaplastic Thyroid Cancers."J.Hum.Genet.. 49(In press). (2004)
• [Publications] 長幡武光: "乳癌術後予後のDNA診断とRNA診断"医薬ジャーナル. 39(3). 72-77 (2003)
• [Publications] 津曲幸二: "乳がんのジェネティクス"最新医学. 58(9). 220-227 (2003)
• [Publications] 音田正光: "乳癌のゲノム解析"分子細胞治療. 2(5). 93-98 (2003)
• [Publications] 浅香晋一: "乳癌における遺伝子研究の現況と展望"乳癌診療Tips & Traps. (印刷中). (2004)
• [Publications] 音田正光: "乳癌の最新医療"先端医療技術研究所. 453 (2003)
• [Publications] Nagai, H.: "Combined Hypermethylation and Chromosome Loss Associated with Inactivation of SSI-1/SOCS-1/JAB Gene in Human Hepatocellular Carcinomas"Cancer Lett. 186(1). 59-65 (2002)
• [Publications] Nagahata, T.: "Correlation of Allelic Losses and Clinicopathological Factors in 504 Primary Breast Cancers"Breast Cancer. 9(3). 208-215 (2002)
• [Publications] Iwasaki, H.: "Accuracy of Genotyping for Single Nucleotide Polymorphism Typing Method involving hybridization of Short Allele-Specific Oligonucleotides"DNA Res.. 9(2). 59-62 (2002)
• [Publications] Harada, H.: "Genomic structure and eight novel exonic polymorphisms of human N-cadherin gene"J. Hum. Genet.. 47(6). 330-332 (2002)
• [Publications] Yoshida, S.: "Head-to-head Juxtaposition of Fas-Associated Phosphatase-1(FAP-1) and c-Jun NH_2-terminal Kinase 3(JNK3) genes : genomic structure and five polymorphisms of FAP-1 gene"J. Hum. Genet.. 47(11). 614-619 (2002)
• [Publications] Shimizu, M.: "Universal Fluorescent Labeling (UFL) Method for Automated Microsatellite Analysis"DNA Res.. 9(5). 173-178 (2002)
• [Publications] Harada. H.: "Down-regulation of a Novel Gene, DRLM, in human Liver Malignancy from 4q22 That Encodes an NAP-like Protein"Gene. 296(1-2). 171-177 (2002)
• [Publications] Tsuneizumi, M.: "A highly polymorphic CA repeat marker at the EBAG9/RCAS1 locus on 8q23 that detected frequent multiplication in breast cancer"Annals Hum. Bio.. 29(4). 457-460 (2002)
• [Publications] Watanabe, T.: "Differentially regulated genes as putative targets of amplifications at 20qin ovarian cancers"Jpn. J. Cancer. Res.. 93(10). 1114-1122 (2002)
• [Publications] Shinohara, Y.: "Three TNFα single nucleotide polymorphisms in the Japanese population"An. Hum. Bio.. 29(5). 579-583 (2002)
• [Publications] Nakata, T.: "Differential Expression of Multiple Isoforms of the ELKS mRNAs Involved in a Papillary Thyroid Carcinoma"Genes, Chrom. Cancer. 35(1). 30-37 (2002)
• [Publications] Harada, H.: "Genomic Structure of the Human NLK(nemo-like kinase) Gene and Analysis of its Promoter Region"Gene. 285(1-2). 175-182 (2002)
• [Publications] Nakajima, T.: "Nucleotide Diversity and Haplotype Structure of the Human Angiotensinogen Gene in Two Populations"Am. J. Hum. Genet.. 70(1). 108-123 (2002)
• [Publications] Tsuneizumi, M.: "Association of Allelic loss at 8p22 with Poor prognosis among Breast Cancers Cases treated with high-dose adjuvant chemotherapy"Cancer Lett.. 180(1). 75-82 (2002)
• [Publications] Fujiwara, H.: "Association of common missense changes in ELAC2 (HPC2) with prostate cancer in a Japanese case-control series"J. Hum. Genet.. 47(12). 641-648 (2002)
• [Publications] Nagahata, T.: "Molecular Diagnosis for Breast Cancer"Jpn. Med. Assoc. J.. 45. 265-260 (2002)
• [Publications] Yasui, K.: "TFDP1, CUL4A, and CDC16 Identified as Targets for Amplification at 13q34 in Hepatocellular Carcinomas"Hepatology. 35(6). 1476-1484 (2002)
• [Publications] Nagai, H.: "Hypermethylation Associated with Inactivation of the SOCS-1 Gene, a JAK/STAT inhibitor, in Human Hepatoblastomas"J. Hum. Genet.. 48(2). 65-69 (2002)
• [Publications] Nagai, H.: "DNA Alterations during Multi-step Development of Human Hepatocellular Carcinomas Revealed by Laser Capture Microdissection"Hepatology Res.. (in press). (2002)
• [Publications] Nagai, H.: "Down-regulation in Human Cancers of DRHC, a Novel Helicase-like Gene from 17q25.1 That Inhibit Cell Growth"Cancer Lett.. (in press). (2003)
• [Publications] 岩崎公典: "ゲノム研究各論〜DNAチップ、マイクロアレイ〜"分子心血管病. 3(3). 109-114 (2002)
• [Publications] 永井尚生: "肝硬変における遺伝子発現異常の解析"消化器科. 34(1). 64-68 (2002)
• [Publications] 永井尚生: "癌の遺伝要因の解明と現状"医学のあゆみ. 202(10). 869-876 (2002)
• [Publications] Kitamura, Y., Emi, M.et al.: "Allelotyping of Follicular Thyroid Carcinoma : Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q"J. Clin. Endocrinol. Metab.. 86. 4268-4272 (2001)
• [Publications] Tsuneizumi, M., Emi, M.et al.: "Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers"Clin. Cancer Res.. 7. 3526-3532 (2001)
• [Publications] Haga, S., Emi, M.et al.: "Association of allelic losses aqt 3p25.1, 13q12, or 17p13.3 with poor prognosis in breast cancers with lymph node metastasis"Jpn. J. Cancer Res.. 92,. 1199-1206 (2001)
• [Publications] Kurose, K., Emi, M.et al.: "Three aberrent splicing variants of the HMGIC gene transcribed in uterine leiomyomas"Genes, Chrom. Cancer.. 30. 212-217 (2001)
• [Publications] Hirano, A., Emi, M.et al.: "Allelic Losses as Prognostic Markers for Breast Cancers"Int. J. Clin. Oncol.. 6. 6-12 (2001)
• [Publications] Hirano, A., Emi, M.et al.: "Allelic Loses of loci at 3p25.1, 8p22, 13q12, 17p13.3 and 22q13 Correlate with Postoperative Recurrence in Breast Cancer"Clin. Cancer Res.. 7(ほか英文原著31本). 876-882 (2000)
• [Publications] 長幡武光, 江見充: "乳癌の遺伝子診断 (特集-「乳癌診断・治療の現状と展望」)"日本医師会雑誌. 1731-1734 (2001)
• [Publications] 平野明, 江見充: "乳癌の遺伝子診断-予防医学のミレニアム"医学のあゆみ. 233-236 (2001)
• [Publications] Ito,K.,Emi,M. et al.: "Association of Allelic Loss on 1q, 4p, 7q, 9p, 9q, and 16q with Postoperative Death in Papillary Thyroid Carcinoma."Clin.Cancer Res.. 6. 1819-1825 (2000)
• [Publications] Utada,Y.,Emi,M. et al.: "Allelic Loss at 1p34-36 Predicts Poor Prognosis in Node-negative Breast Cancer."Clin.Cancer Res.. 6. 3193-3198 (2000)
• [Publications] Nakamura,Y.,Emi,M. et al.: "Loss of heterozygosity at 3p24-p25 as a prognostic factor in breast cancer."Cancer Lett.. 152. 63-69 (2000)
• [Publications] Moriyama,Y.,Emi,M. et al.: "New Target Region of Allelic Loss in Hepatocellular Carcinomas within a l-cM Interval on Chromosome 6q23."J.Hepatol. 32. 85-90 (2000)
• [Publications] Inazawa,J.,Emi,M. et al.: "Genomic structure and chromosomal mapping of the human Site-1 protease (S1P) gene."J.Hum.Genet.. 45. 212-217 (2000)
• [Publications] Kodama,T.,Emi,M. et al.: "Genomic structure of the gene encoding human 3-hydroxy-3-methyl-glutaryl coenzyme A reductase : comparison of exon/intron organization of sterol-sensing domains amang four related genes."J.Hum.Genet.. 45. 284-289 (2000)