小儿肉瘤中胰岛素样生长因子2、刺猬因子及融合基因表达谱的研究

Investigation of IGF2, Hedgehog and fusion gene expression profiles in pediatric sarcomas.

作者信息

de Souza Robson Ramos, Oliveira Indhira Dias, del Giúdice Paniago Mario, Yaoita Fernando Hideki Kato, Caran Eliana Maria Monteiro, Macedo Carla Renata Pacheco Donato, Petrilli Antonio Sergio, Abib Simone de Campos Vieira, de Seixas Alves Maria Teresa, de Toledo Silvia Regina Caminada

机构信息

Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Department of Structural and Functional Biology, Federal University of São Paulo, São Paulo, SP, Brazil.

Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil.

出版信息

Growth Horm IGF Res. 2014 Aug;24(4):130-6. doi: 10.1016/j.ghir.2014.04.002. Epub 2014 Apr 16.

DOI:10.1016/j.ghir.2014.04.002

PMID:24846856

Abstract

UNLABELLED

The childhood sarcomas are malignant tumors with high mortality rates. They are divided into two genetic categories: a category without distinct pattern karyotypic changes and the other category showing unique translocations that originate gene rearrangements. This category includes rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS). Diverse studies have related development genes, such as; IGF2, IHH, PTCH1 and GLI1 and sarcomatogenesis.

OBJECTIVE

To characterize the RMS, ES and SS rearrangements, we quantify the expression of IGF2 IHH, PTCH1 and GLI1 genes and correlate molecular data with clinical parameters of patients.

DESIGN

We analyzed 29 RMS, 10 SS and 60 ES tumor samples by RT-PCR (polymerase chain reaction-reverse transcription) and qPCR (quantitative PCR).

RESULTS

Among the samples of ARMS, 50% had rearrangements of PAX3/7-FOXO1, 60% of ES samples were EWS-FLI1 positive and 90% of SS samples were positive for SS18-SSX1/2. In relation to the control reference samples (QPCR Human Reference Total RNA-Stratagene, Human Skeletal Muscle Total RNA-Ambion, Universal RNA Human Normal Tissues-Ambion), RMS samples showed a high IGF2 gene expression (p<0.0001). Moreover, ES samples showed a low IGF2 gene expression (p<0.0001) and high IHH (p<0.0001), PTCH1 (p=0.0173) and GLI1 (p=0.0113) gene expressions.

CONCLUSIONS

The molecular characterization of IGF and Hedgehog pathway in these pediatric sarcomas may collaborate to enable a better understanding of the biological behavior of these neoplasms.

摘要

未标注

儿童肉瘤是死亡率很高的恶性肿瘤。它们分为两个基因类别：一类没有明显的核型变化模式，另一类显示出独特的易位，这些易位会引发基因重排。这一类别包括横纹肌肉瘤（RMS）、尤因肉瘤（ES）和滑膜肉瘤（SS）。各种研究已将发育基因，如胰岛素样生长因子2（IGF2）、印度刺猬蛋白（IHH）、音猬因子1（PTCH1）和胶质瘤相关癌基因1（GLI1）与肉瘤发生联系起来。

目的

为了表征RMS、ES和SS的重排情况，我们对IGF2、IHH、PTCH1和GLI1基因的表达进行定量，并将分子数据与患者的临床参数相关联。

设计

我们通过逆转录聚合酶链反应（RT-PCR）和定量聚合酶链反应（qPCR）分析了29个RMS、10个SS和60个ES肿瘤样本。

结果

在腺泡状横纹肌肉瘤（ARMS）样本中，50%存在PAX3/7-FOXO1重排，60% 的ES样本EWS-FLI1呈阳性，90% 的SS样本SS18-SSX1/2呈阳性。与对照参考样本（定量PCR人类参考总RNA - Stratagene、人类骨骼肌总RNA - Ambion、通用RNA人类正常组织 - Ambion）相比，RMS样本显示出较高的IGF2基因表达（p<0.0001）。此外，ES样本显示出较低的IGF2基因表达（p<0.0001）以及较高的IHH（p<0.0001）、PTCH1（p = 0.0173）和GLI1（p = 0.0113）基因表达。