A Cytogenetical analysis of the malignant transformation of primary intracranial germ cell tumor

原发性颅内生殖细胞肿瘤恶变的细胞遗传学分析

• 批准号: 09470291
• 负责人: WASHIYAMA Kazuo
• 金额: $ 8.32万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470291/
• 关键词: intracranial; germ cell tumor; transformatin; tumor supressor gene; p53; chromosome; cell line; 松果体部腫瘍; 胚細胞性腫瘍; intracranial gem cell tumor; cytokeratin; malignant transformation; intracranial germ cell tumor; Cytokeratin; tumor suppressor g

To investigate the details of the malignant transformation of intracranial germ cell tumors, we established 4 cell lines derived from surgical or autopsied specimen of brain tumors, and studied cytogenetic charactors and tumor supressor gene alterations.Cytokeratin was expressed in 4 of 4. HCG was expressed in 1 of 4. AFP was expressed in 3 of 4. It was suggested that they corresponded to one of choricarcinoma, one of embryonal carcinoma, and two of yolk tumor each.Cytogenetic investigation of the tumor diagnosed as choriocarcinoma revealed a highly abnormal chromosomal pattern. A chromosomal number in the hypotetraploid/hypertetraploid range was found. We analyzed 10 metaphases with the following modal composite karyotype: 88-94 <4n>, XX, +X, -Y, -Y, add (1) (p11), add (2) (q21), -2, add (2)(p25), -3, add (3) (p21), add (3), add (4) (p11), add (4) (ql 1), add (4), -5, -5, -5, del (6) (p21p23), add (7) (ql1), -8, -8, add (8) (q2?), add (9) (ql1), -10, del (10) (q24), del (10), -12, add (12) (p13), add (12), -13, add (14) (q21), -15, -16, -18, -18, t (18; 20) (p10; p10), t (18; 20) (p10; p10), +21, +21, -22, +13 mar. These karyotypes were shown by trypsin G-banding and confirmed by multi-colored FISH analysis.The mutation of p53 gene was not detected by PCR-SSCP method as far as the analysis from exon 4 to exon 9. p16 and p14 genes were detected normally by Southern blot analysis using p16 exons 1 to 3 and p14 exon probes. Thus, the major 2 pathways of tumor suppression seemed to be normal though Rb gene was not examined.

为探讨颅内生殖细胞肿瘤恶变的具体情况，我们建立了4株来源于手术或尸检脑肿瘤标本的细胞系，并对其细胞遗传学特征和抑癌基因的改变进行了研究。4例中1例表达HCG。4例中3例AFP阳性。结果表明，它们分别为绒毛膜癌、胚胎癌和卵黄瘤各1例，诊断为绒毛膜癌的细胞遗传学检查显示染色体异常。我们分析了10个中期分裂相的典型复合核型：88-94<4n>，XX，+X，-Y，-Y，add（1）（p11），add（2）（q21），-2，add（2）（p25），-3，add（3）（p21），add（3），add（4）（p11），add（4）（ql 1），add（4），-5，-5，-5，del（6）（p21p23），add（7）（ql 1），-8，-8，add（8）（q2？），add（9）（ql1），-10，del（10）（q24），del（10），-12，add（12）（p13），add（12），-13，add（14）（q21），-15，-16，-18，-18，t（18; 20）用胰蛋白酶G显带和多色荧光原位杂交分析证实了这些染色体核型，而PCR-SSCP分析未发现p53基因第4 ~ 9外显子的突变。用p16外显子1 ~ 3和p14外显子探针进行Southern印迹分析，正常检测p16和p14基因。因此，尽管未检测Rb基因，但肿瘤抑制的两个主要途径似乎是正常的。

项目成果

Feng, X. -L., Usui, H., Fujita, T., Ichikawa, T., Katagiri, T., Washiyama, K., Kumanishi, T.: "Postnatal developmental changes of NSE and NNE mRNA expression in rat pineal gland : in situ hybridization histochemistry"J. Pineal Res.. 24. 108-116 (1998)

Feng, X. -L., Usui, H., Fujita, T., Ichikawa, T., Katagiri, T., Washiyama, K., Kumanishi, T.：“大鼠 NSE 和 NNE mRNA 表达的产后发育变化

Tsumanuma, I.: "Clinicopathological Study of Pineal Parenchymal Tumors; Correlation between histopathological features, proliferative potential, and prognosis"Brain Tumor Pathology. 16(2). 61-68 (1999)

Tsumanuma, I.：“松果体实质肿瘤的临床病理学研究；组织病理学特征、增殖潜力和预后之间的相关性”脑肿瘤病理学。

鷲山 和雄: "松果体実質細胞性腫瘍と神経成長因子受容体"医学のあゆみ. 192. 781-784 (1999)

Kazuo Washiyama：“松果体实质肿瘤和神经生长因子受体”医学史 192. 781-784 (1999)。

Zhang, S-J., Endo, S., Ichikawa, T., Yoshimura, J., Onda, K., Tanaka, R., Washiyama, K. and Kumanishi, T.: "Rare-type mutations of MMAC1 tumor suppressor gene in human glioma cell lines and their tumors of origin"Jpn. J. Cancer Res.. 90. 934-941 (1999)

张，S-J.，Endo，S.，Ichikawa，T.，Yoshimura，J.，Onda，K.，Tanaka，R.，Washiyama，K.和Kumanishi，T.：“MMA​​C1抑癌基因的罕见突变

Washiyama, K.: "Establishment of Four Cell Lines Derived from Human Intracranial Germ Cell Tumors"Brain Pathology. 7(4). 1189 (1997)

Washiyama, K.：“从人颅内生殖细胞肿瘤衍生的四种细胞系的建立”脑病理学。