Altered expression of cell-cycle regulatory genes and proteins in malignant bone and soft tissue tumors

恶性骨和软组织肿瘤中细胞周期调节基因和蛋白质表达的改变

• 批准号: 15590304
• 负责人: ODA Yoshinao
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590304/
• 关键词: cell-cycle regulatory gene; cell-cycle regulatory protein; malignant bone and soft tissue tumor; p16; p53; p21; RB1; CHFR; 悪性末梢神経鞘腫瘍; p14; メチル化; チェックポイント機能; 染色体異常; Rb遺伝子; LOH解析; p16遺伝子; 遺伝子メチル化; 粘液型脂肪肉腫; 脱分化型脂肪肉腫; マイクロサテライト不安定性; E2F-1

We have carried out extensive investigations concerning altered expression of cell-cycle regulatory genes and proteins in several kinds of malignant bone and soft tissue tumors and the following results have been obtained.Leiomyosarcoma ; Decreased expression of p16 was significantly poor prognostic factor in both univariate and multivariate analysis. Promoter methylation was shown to have a strong association with inactivation of p16INK4a gene. (Kawaguchi et al. J Pathol 2003) Alveolar soft part sarcoma (ASPS) ; Inactivation of hMLH1/hMSH2 of DNA mismatch repair genes seems to have an important role to play in the mutagenesis of the tumor-suppressor genes in ASPS. (Saito et al. Hum Pathol 2003) Myxofibrosarcoma ; Reduced expression of p21 could be considered a new parameter to be evaluated, along with classical clinicopathologic prognostic factors, for identifying those at high risk for myxofibrosarcoma. (Oda et al. Hum Pathol 2003) Giant cell tumor of bone ; TGF-beta-IIR and p27 expr … More ession were concordantly decreased and this result supports the possibility that these two factors may play an important role in cell proliferation of this tumor. (Kawaguchi et al. Hum Pathol 2004) Dermatofibrosarcoma protuberans (DFSP) ; Microsatellite instability and p53 mutations are involved in tumor progression of DFSP to fibrosarcoma as early and late events, respectively. (Takahira et al. Hum Pathol 2004) Rhabdomyosarcoma ; p53 overexpression may be related to tumor progression because tumors with p53 overexpression have a high proliferative activity. Alveolar type had a significantly higher both mitotic rate and E2F-1 labeling indices when compared with the embryonal type. (Takahashi et al. Mod Pathol 2004) Clear cell sarcoma (CCS) ; All tumors with genetic alterations of the p16INK4a/p14ARF or p53 gene showed a high mitotic rate or tumor necrosis. These alterations were considered to be influential in the poor prognosis of CCS patients. (Takahira et al. Cancer Sci 2004) Dedifferentiated liposarcoma ; Dedifferentiated component more frequently harbored LOH, mutation or promoter methylation of RB1 gene as compared with those in the well-differentiated component. These results suggests that RB protein has a major roel to play in dedifferentiation. (Takahira et al. Mod Pathol 2005) Myxoid/round cell liposarcoma (MLS/RCLS) ; In MLS/RCLS, reduction of p14 protein expression and p53 mutation were related to poor prognosis. These alterations are correlated with the presence of round cell component, which is one of the strong adverse prognostic factors. Accordingly, the p14ARF/p53 pathway may contribute to the presence of round cell component and malignant progression in this tumor. (Oda et al. J Pathol 2005) Malignant peripheral nerve sheath tumor (MPNST) ; Decreased expression of checkpoint with forkhead-associated domain and ring finger (CHFR) was significantly correlated with a high mitotic count, a high ki-67-labeling index and a poor prognosis in MPNST. These results support the assertion that CHFR functions as an inhibitor of tumor proliferation. (Kobayashi et al. Mod Pathol, in press) Less

我们对几种恶性骨和软组织肿瘤中细胞周期调节基因和蛋白质表达的改变进行了广泛的研究，并获得了以下结果：平滑肌肉瘤;在单变量和多变量分析中，p16表达下降是显着不良预后因素。启动子甲基化与p16 INK 4a基因失活密切相关。（川口等人，J Pathol 2003）肺泡软组织肉瘤（ASPS）; DNA错配修复基因的hMLH 1/hMSH 2失活似乎在ASPS中肿瘤抑制基因的诱变中起重要作用。（Saito et al. Pathol 2003）粘液纤维肉瘤; p21表达降低可被视为一个新的待评价参数，沿着经典临床病理学预后因素，用于鉴别粘液纤维肉瘤高风险患者。(Oda 2003）骨巨细胞瘤; TGF-β-IIR和p27表达 ...更多信息 结果表明，这两种因子在该肿瘤的细胞增殖中可能起重要作用。（川口et al. Pathol 2004）隆突性皮肤纤维肉瘤（DFSP）;微卫星不稳定性和p53突变分别作为早期和晚期事件参与DFSP向纤维肉瘤的肿瘤进展。（Takahira et al. Pathol 2004）横纹肌肉瘤; p53过表达可能与肿瘤进展相关，因为p53过表达的肿瘤具有高增殖活性。肺泡型细胞的有丝分裂率和E2 F-1标记指数均显著高于胚胎型细胞。（Takahashi et al. Mod Pathol 2004）透明细胞肉瘤（CCS）;所有p16 INK 4a/p14 ARF或p53基因发生遗传改变的肿瘤均显示高有丝分裂率或肿瘤坏死。这些改变被认为是CCS患者预后不良的影响。（Takahira et al. Cancer Sci 2004）去分化脂肪肉瘤;与分化良好的成分相比，去分化成分更频繁地具有RB 1基因的洛、突变或启动子甲基化。这些结果表明RB蛋白在去分化中起主要作用。（Takahira et al. Mod Pathol 2005）粘液样/圆细胞脂肪肉瘤（MLS/RCLS）;在MLS/RCLS中，p14蛋白表达减少和p53突变与预后不良相关。这些改变与圆形细胞成分的存在相关，这是一个强有力的不良预后因素。因此，p14 ARF/p53通路可能有助于该肿瘤中圆形细胞成分的存在和恶性进展。(Oda恶性外周神经鞘瘤（MPNST）;具有叉头相关结构域和无名指的检查点（CHFR）的表达降低与MPNST中的高有丝分裂计数、高ki-67标记指数和不良预后显著相关。这些结果支持CHFR作为肿瘤增殖抑制剂的断言。（小林等. Mod Pathol，出版中）减

项目成果

Alterations of cell cycle regulators in myxofibrosarcoma.

粘液纤维肉瘤细胞周期调节因子的改变。

• 发表时间: 2003
• 期刊: Human Pathology 34
• 作者: Oda Y;Tamiya S;et al.
• 通讯作者: et al.

Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas

• DOI: 10.1016/j.humpath.2005.01.017
• 发表时间: 2005-04-01
• 期刊: HUMAN PATHOLOGY
• 影响因子: 3.3
• 作者: Kawaguchi, K;Oda, Y;Tsuneyoshi, M
• 通讯作者: Tsuneyoshi, M

Aberrant expression of CHFR in malignant peripheral nerve sheath tumors

• DOI: 10.1038/modpathol.3800548
• 发表时间: 2006-04-01
• 期刊: MODERN PATHOLOGY
• 影响因子: 7.5
• 作者: Kobayashi, C;Oda, Y;Tsuneyoshi, M
• 通讯作者: Tsuneyoshi, M

Yamamoto H, Oda Y et al.: "p53 mutation and MDM2 amplification in inflammatory myofibroblastic tumors."Histopathology. 42. 431-439 (2003)

Yamamoto H、Oda Y 等人：“炎症性肌纤维母细胞肿瘤中的 p53 突变和 MDM2 扩增。”组织病理学。

Alterations of the RB1 gene in dedifferetiated liposarcoma.

去分化脂肪肉瘤中 RB1 基因的改变。

• 发表时间: 2005
• 期刊: Modern Pathology 18
• 作者: Takahira T;Oda Y;Tamiya S;et al.
• 通讯作者: et al.