髓母细胞瘤中半胱天冬酶8基因的缺失及异常CpG岛甲基化

Deletion and aberrant CpG island methylation of Caspase 8 gene in medulloblastoma.

作者信息

Gonzalez-Gomez Pilar, Bello M Josefa, Inda M Mar, Alonso M Eva, Arjona Dolores, Amiñoso Cinthia, Lopez-Marin Isabel, de Campos Jose M, Sarasa Jose L, Castresana Javier S, Rey Juan A

机构信息

Laboratorio de Oncogenética Molecular y Epigenética del Cáncer, Departamento de C. Experimental, Unidad de Investigación, Hospital Universitario La Paz, Paseo Castellana 261, 28046 Madrid, Spain.

出版信息

Oncol Rep. 2004 Sep;12(3):663-6.

PMID:15289853

Abstract

Aberrant methylation of promoter CpG islands in human genes is an alternative genetic inactivation mechanism that contributes to the development of human tumors. Nevertheless, few studies have analyzed methylation in medulloblastomas. We determined the frequency of aberrant CpG island methylation for Caspase 8 (CASP8) in a group of 24 medulloblastomas arising in 8 adult and 16 pediatric patients. Complete methylation of CASP8 was found in 15 tumors (62%) and one case displayed hemimethylation. Three samples amplified neither of the two primer sets for methylated or unmethylated alleles, suggesting that genomic deletion occurred in the 5' flanking region of CASP8. Our findings suggest that methylation commonly contributes to CASP8 silencing in medulloblastomas and that homozygous deletion or severe sequence changes involving the promoter region may be another mechanism leading to CASP8 inactivation in this neoplasm.

摘要

人类基因启动子CpG岛的异常甲基化是一种导致人类肿瘤发生的替代性基因失活机制。然而，很少有研究分析髓母细胞瘤中的甲基化情况。我们测定了一组24例髓母细胞瘤中Caspase 8（CASP8）基因启动子CpG岛的异常甲基化频率，这些髓母细胞瘤患者包括8名成人和16名儿童。在15例肿瘤（62%）中发现了CASP8的完全甲基化，1例显示半甲基化。3个样本未能扩增出甲基化或未甲基化等位基因的两组引物，提示CASP8基因5'侧翼区域发生了基因组缺失。我们的研究结果表明，甲基化通常导致髓母细胞瘤中CASP8基因沉默，纯合缺失或涉及启动子区域的严重序列改变可能是导致该肿瘤中CASP8失活的另一种机制。