Genetic diagnogis of breast cancer

乳腺癌的基因诊断

• 批准号: 10671573
• 负责人: EMI Mitsuru
• 金额: $ 0.64万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671573/
• 关键词: Uterine myoma; gene fusion; HMGI-C; Chromosome 12; translocation; COSVIc; 子宮平滑筋腫; 間葉系良性腫瘍; 第12番染色体長腕; 遺伝子の再構成; 融合遺伝子

Cytogenetic analyses have shown that aberrations involving 12q13-15 are frequent chromosomal changes in a variety of human benign mesenchymal tumors, e.g., pleomorphic adenomas of the parotid gland, pulmonary chondroid hamartomas, lipomas, and uterine leiomyomas. Recently, the high-mobility group protein gene HMGIC was identified as the target gene affected by the 12q13-15 aberrations. Using 3' rapid amplification of cDNA ends experiments, we isolated novel ectopic sequences fused to HMGIC in a uterine leiomyoma. Cloning of the fusion cDNA identified the human cytochrome c oxidase subunit Vic (COX6c) gene on 8q22-23 as the fusion partner of HMGIC. Nucleotide sequences of the fusion transcript revealed that the first three exons of the HMGIC gene, encoding the three DNA binding domains, was fused to the exon 2 of the COX6C gene. The identification of a gene rearrangement suggests a role for HMGIC in tumorigenesis of uterine leiomyoma, and suggests a possible involvement of HMGIC in mesenchymal differentiation.

细胞遗传学分析表明，涉及12 q13 -15的畸变是多种人类良性间叶肿瘤中常见的染色体变化，例如，腮腺多形性腺瘤、肺软骨样错构瘤、脂肪瘤和子宫平滑肌瘤。最近，高迁移率族蛋白基因HMGIC被确定为受12 q13 -15畸变影响的靶基因。利用cDNA末端3'快速扩增实验，我们在子宫平滑肌瘤中分离到与HMGIC融合的新的异位序列。融合cDNA的克隆鉴定了位于8 q22 -23上的人细胞色素c氧化酶亚基维克（COX 6c）基因作为HMGIC的融合伴侣。融合转录本的核苷酸序列显示，HMGIC基因的前三个外显子，编码三个DNA结合结构域，融合到COX 6C基因的外显子2。基因重排的鉴定表明HMGIC在子宫平滑肌瘤的肿瘤发生中的作用，并表明HMGIC可能参与间充质分化。

项目成果

Nakata,T. et al.: "Fusion of a Novel Gene, ELKS, to c-ret due to Translocation t(10 ; 12)(q11 ; p13) in a Papillary Thyroid Carcinoma." Genes., Chrom. Cancer.25(in press). (1999)

中田，T.

Nakata T, Kitamura Y, Shimizu K, Tanaka S, Fujimori M, Yokoyama S, Ito K. & Emi M: "Fusion of a Novel Gene, ELKS, to c-ret due to Translocation t (10 ; 12) (q11 ; 13) in a Papillary Thyroid Carcinoma."Genes, Chrom. Cancer.. 25. 97-103 (1999)

中田 T、北村 Y、清水 K、田中 S、藤森 M、横山 S、伊藤 K。

Koyama M, Ito M, Nagai H, Emi M, Moriyama: "Inactivation of Both Alleles of the DPC4/SMAD4 Gene in Advanced Colorectal Cancers : Identification of Seven Novel Somatic Mutations in Tumors from Japanese Patients."Mutation Res. Genom.. 406. 71-77 (1999)

Koyama M、Ito M、Nagai H、Emi M、Moriyama：“晚期结直肠癌中 DPC4/SMAD4 基因的两个等位基因失活：日本患者肿瘤中七种新的体细胞突变的鉴定。”突变研究。

Koyama,M.,Emi,M. et al.: "Inactivation of Both Alleles of the DPC4/SMAD4 Gene in Advanced Colorectal Cancers: Identification of Seven Novel Somatic Mutations in Tumors from Japanese Patients."Mutation Res. Genom.. 406. 71-77 (1999)

小山，M.，惠美，M.

Kurose K, Araki T, Matsunaka T, Takada Y, & Emi M.: "Variant manifestation of Cowden Disease in Japan : Hamartomatous polyposis of the Digestive Tract with Mutation of the PTEN Gene."Am. J. Hum. Genet.. 64. 308-310 (1999)

黑濑 K、荒木 T、松中 T、高田 Y、